S100P在结直肠癌中异常表达的临床意义及其调控机制
摘要
研究背景
结直肠癌是世界范围内常见的恶性肿瘤,在我国结直肠癌居癌症致死因素的第四位。尽管近年来手术方式和辅助治疗手段不断发展,结直肠癌患者的生存率仍旧不理想。深入研究结直肠癌的分子机制,寻找理想的用于早期诊断或判断预后的结直肠癌肿瘤标志物,具有重要的临床意义。近年来关于S100P在肿瘤组织中的异常表达逐渐受到重视,其在多种肿瘤中均有异常表达,且与肿瘤的生长、浸润及转移密切相关,对部分肿瘤的诊断分型及预后判断均有一定价值。但是,S100P在结直肠癌中高表达的临床价值尚未明确。
研究目的
明确S100P在结直肠癌组织中高表达的临床意义,探讨调控S100P基因表达的表观遗传学机制。研究结直肠癌患者血清S100P水平是否增高及其临床价值。
实验方法
选取我院自2003年7月至2006年7月手术切除的96例散发性结直肠癌及配对正常结直肠组织标本与其中76例患者的术前血清标本。统计所有患者的临床病理资料,并进行为期30～65个月的术后随访。
采用免疫印迹法和实时定量逆转录PCR的方法检测S100P蛋白和mRNA在结直肠癌组织与正常对照组织以及结直肠癌细胞系中的表达。并与患者的临床病理资料和预后相关资料进行统计分析。
通过对基因组经亚硫酸氢盐修饰后直接测序的方法明确S100P基因启动子区甲基化与基因表达的相关性。建立荧光实时定量甲基化特异性PCR的方法检测结直肠癌组织与正常对照组织以及结直肠癌细胞系中S100P基因启动子区甲基化状态,并与S100P基因的表达和患者临床资料进行相关分析。
通过ELISA方法检测结直肠癌患者及健康正常人血清S100P水平,并结合患者临床病理资料与预后相关资料评价结直肠癌患者术前血清S100P测定的诊断价值和预后价值。
实验结果
96例散发性结直肠癌患者中男性61例,女性35例,平均年龄62.4±1.2岁;右半结肠癌29例,左半结肠癌17例,直肠癌50例。S100P蛋白在结直肠癌组织中表达的阳性率为63.0%(51/81),显著高于正常对照组织(4.9%,P=8.13×10_(-15));S100P mRNA在结直肠癌组织中的表达也显著高于配对的正常对照组织(P=0.005)。通过对基因组经亚硫酸氢盐修饰后直接测序的方法检测S100P基因启动子区甲基化状态在结直肠癌肿瘤细胞系和组织中与S100P mRNA的表达显著相关(P值分别为0.002;0.039)。通过荧光实时定量甲基化特异性PCR的方法检测S100P基因启动子区甲基化状态在结直肠癌肿瘤细胞系和组织中与S100P mRNA的表达也有显著的相关性(P值分别为0.001;5.0×10~(-6))。
结直肠癌组织中S100P蛋白的表达与肿瘤的原发部位显著相关(P=0.008),从右半结肠、左半结肠至直肠,S100P蛋白的阳性率分别为42.3%、61.5%、76.2%。S100P蛋白的表达与结直肠的临床分期无显著性相关(P=0.524)。S100P mRNA在结直肠癌中的表达与肿瘤的原发部位、临床分期等临床特征并无显著的相关性。S100P基因启动子区去甲基化状态的定量值在直肠癌显著高于结肠癌(P=0.007),且其随着结直肠癌分化程度的减低有逐渐减低的趋势(P=0.098)。在Ⅰ～Ⅲ期的结直肠癌患者中,组织S100P阴性患者的预后有优于组织S100P阳性患者的趋势(P=0.056)。
结直肠癌患者术前血清S100P水平显著高于正常人(P=7.4x10~(-9))。血清S100P诊断结直肠癌的敏感度为38.2%,相对于正常人的特异度为91.9%,联合血清CEA检测在结直肠癌患者中的阳性率可达64.4%。结直肠癌患者血清S100P水平有随肿瘤分期逐渐升高的趋势(P=0.050),其阳性率分别为Ⅰ期25.0%、Ⅱ期30.8%、Ⅲ期44.4%、Ⅳ期54.5%。术前血清S100P水平是结直肠癌患者长期生存的独立影响因素(P=0.023)。术前血清S100P阳性的结直肠癌患者的5年生存率为52.3%,而术前血清S100P阴性患者的5年生存率为81.4%(P=0.005)。在调整了临床分期的影响后,术前血清S100P升高的结直肠癌患者死亡的风险是血清S100P正常者的3.6倍。
实验结论
S100P蛋白与mRNA在结直肠癌组织中的表达显著高于配对的正常结直肠组织,S100P蛋白的表达与肿瘤的原发部位显著相关,并与患者的生存时间呈负相关趋势。S100P基因启动子区的甲基化状态与基因表达密切相关,可能在一定程度上参与调控了S100P基因的表达。结直肠癌患者术前血清S100P水平显著高于健康正常人群,并与生存时间显著相关,其水平升高提示患者预后不良。与血清CEA联合检测可提高诊断结直肠癌的敏感性。
Background:Colorectal cancer(CRC) is one of the most common types of malignant tumors worldwide.In China,CRC is the 4th leading cause of cancer-related mortality.Although great advances have been made in the diagnosis and treatment of this cancer,the survival rate of CRC patients is not improved profoundly.It has important clinical significance to put insights into the molecular mechanism of CRC and to search for the ideal markers for the early diagnosis and prognosis.In recent years,researchers has paid close attention to S100P,which has abnormal expression in many tumors and may contribute to the growth、infiltration and metastasis of tumor cells.The expression of S100P is related to the diagnosis or prognosis in some tumors.It has not been identified,however,the clinical value of the high expression of SIOOP in CRC.
Objective:To identify the clinical significance of S100P high expression in CRC tissue,and to investigate Epigenetic mechanisms of S100P expression. Moreover,the serum level of S100P in CRC and its clinical value is to be studied.
Methods:The postoperative tumor tissue samples and their paired normal colorectal tissue from 96 patients and preoperative serum specimens from 76 patients with sporadic CRC in our hospital were collected from July 2003 to July 2006.The clinical pathologic data of these patients were integrated,with the follow-up period of 30 to 65 months.
Western blot and real-time quantitative reverse-transcription PCR were performed for detecting the expression of S100P protein and mRNA in CRC tissue and in colorectal cancer cell lines.The data of the expression of S100P protein and mRNA were analyzed and correlated with the clinical pathologic information.
The correlation of S100P promoter region methylation and S100P gene expression was identified by Bisulphite Sequencing PCR(BSP).The method of fluorescence real time Quantitative Methylation Specific PCR(QMSP) was set up to detect the methylation state of S100P promoter region in CRC tissue and in colorectal cancer cell lines.The date from BSP and QMSP were then correlated with the S100P gene expression and clinical data.
Enzyme linked immunosorbent assay(ELISA) was used for detecting the serum level of S100P in patients with CRC and normal controls.The results were correlated with the clinical data to evaluate the diagnosis and prognosis value of the preoperative serum S100P level in patients with CRC.
Results:Of 96 patients with sporadic CRC involved in this study,61 were males and 35 were females,including 29 right hemicolon cancers,17 left hemicolon cancers and 50 rectal cancers.The average age was 62.4±1.2 years.63.0%(51/81) of CRC tissue express S100P protein,significantly higher than the paired control group(4.9%,P=8.13×10~(-15)).The expression of S100P mRNA in CRC tissue is also significantly higher than the paired normal group(P=0.005).The methylation state of S100P promoter region detected by BSP was strikingly correlated with the expression of S100P mRNA(P=0.002, 0.039,respectively) in colorectal cancer cell lines and tissue.A similar result was obtained through fluorescence real time QMSP in colorectal cancer cell lines and tissue(P=0.001,5.0×10~(-6),respectively).
The expression of S100P protein in CRC tissue has significant correlation with the primary cancer location.The expressing rate of S100P protein in CRC was 42.3%for right hemicolon,61.5%for left hemicolon,and 76.2%for rectum. The similar relation was not shown between the expression of S100P protein and the clinical stage.However there was no notable correlation between the expression of S100P mRNA and the clinical features of CRC such as primary cancer location and clinical stage.The quantitation of the methylation state of S100P promoter region was significantly higher in rectal cancer than in colon cancer(P=0.007),which also had a gradual downward trend according to the decrease of the tumor differentiation degree(P=0.098).In the CRC patients from stageⅠto stageⅢ,a tendency was shown that the prognosis of patients with S100P protein expression was better than that without expression(P= 0.056).
The preoperative serum level of S100P in CRC patients is significantly higher than normal controls.The sensitivity of serum S100P level for diagnosis of CRC was 38.2%and the specificity was 91.9%compared with the healthy people.Combined test of serum S100P and CEA in CRC had a positive rate up to 64.4%.The preoperative serum S100P level in CRC patients had a tendency to increase as the cancer clinical stage progressing(P=0.050).The positive rate of serum S100P in each stage of CRC was stageⅠ25.0%,stageⅡ30.8%,stageⅢ44.4%and stageⅣ54.5%.The preoperative serum level of S100P was an independent factor of long - term survival(P=0.023) in CRC patients.The 5-year cumulative survival rate of patients with a high preoperative serum S100P level was 52.3%,and the 5-year cumulative survival rate of patients with a normal serum S100P level was 81.4%(P=0.005). If adjusted the influence of clinical stage,the CRC patients with elevated preoperative serum S100P had a 3.6 times increase in the risk of death comparing with those with normal serum S100P levels.
Conclusions:The expression of S100P protein and mRNA in CRC tissue is significantly higher than the paired normal colorectal tissue.The expression of S100P protein is notably correlated with the primary cancer locations,and also has a negative correlation with survival of CRC patients.In some degree,the methylation state of S100P promoter region may regulate the expression of S100P.The preoperative serum S100P level in CRC patients is significantly higher than that in normal controls.Preoperative elevated serum S100P level correlates with a poor prognosis in CRC patients.Combined test of serum S100P and CEA can increase the sensitivity of diagnosis in CRC.
结直肠癌是世界范围内常见的恶性肿瘤,在我国结直肠癌居癌症致死因素的第四位。尽管近年来手术方式和辅助治疗手段不断发展,结直肠癌患者的生存率仍旧不理想。深入研究结直肠癌的分子机制,寻找理想的用于早期诊断或判断预后的结直肠癌肿瘤标志物,具有重要的临床意义。近年来关于S100P在肿瘤组织中的异常表达逐渐受到重视,其在多种肿瘤中均有异常表达,且与肿瘤的生长、浸润及转移密切相关,对部分肿瘤的诊断分型及预后判断均有一定价值。但是,S100P在结直肠癌中高表达的临床价值尚未明确。
研究目的
明确S100P在结直肠癌组织中高表达的临床意义,探讨调控S100P基因表达的表观遗传学机制。研究结直肠癌患者血清S100P水平是否增高及其临床价值。
实验方法
选取我院自2003年7月至2006年7月手术切除的96例散发性结直肠癌及配对正常结直肠组织标本与其中76例患者的术前血清标本。统计所有患者的临床病理资料,并进行为期30～65个月的术后随访。
采用免疫印迹法和实时定量逆转录PCR的方法检测S100P蛋白和mRNA在结直肠癌组织与正常对照组织以及结直肠癌细胞系中的表达。并与患者的临床病理资料和预后相关资料进行统计分析。
通过对基因组经亚硫酸氢盐修饰后直接测序的方法明确S100P基因启动子区甲基化与基因表达的相关性。建立荧光实时定量甲基化特异性PCR的方法检测结直肠癌组织与正常对照组织以及结直肠癌细胞系中S100P基因启动子区甲基化状态,并与S100P基因的表达和患者临床资料进行相关分析。
通过ELISA方法检测结直肠癌患者及健康正常人血清S100P水平,并结合患者临床病理资料与预后相关资料评价结直肠癌患者术前血清S100P测定的诊断价值和预后价值。
实验结果
96例散发性结直肠癌患者中男性61例,女性35例,平均年龄62.4±1.2岁;右半结肠癌29例,左半结肠癌17例,直肠癌50例。S100P蛋白在结直肠癌组织中表达的阳性率为63.0%(51/81),显著高于正常对照组织(4.9%,P=8.13×10_(-15));S100P mRNA在结直肠癌组织中的表达也显著高于配对的正常对照组织(P=0.005)。通过对基因组经亚硫酸氢盐修饰后直接测序的方法检测S100P基因启动子区甲基化状态在结直肠癌肿瘤细胞系和组织中与S100P mRNA的表达显著相关(P值分别为0.002;0.039)。通过荧光实时定量甲基化特异性PCR的方法检测S100P基因启动子区甲基化状态在结直肠癌肿瘤细胞系和组织中与S100P mRNA的表达也有显著的相关性(P值分别为0.001;5.0×10~(-6))。
结直肠癌组织中S100P蛋白的表达与肿瘤的原发部位显著相关(P=0.008),从右半结肠、左半结肠至直肠,S100P蛋白的阳性率分别为42.3%、61.5%、76.2%。S100P蛋白的表达与结直肠的临床分期无显著性相关(P=0.524)。S100P mRNA在结直肠癌中的表达与肿瘤的原发部位、临床分期等临床特征并无显著的相关性。S100P基因启动子区去甲基化状态的定量值在直肠癌显著高于结肠癌(P=0.007),且其随着结直肠癌分化程度的减低有逐渐减低的趋势(P=0.098)。在Ⅰ～Ⅲ期的结直肠癌患者中,组织S100P阴性患者的预后有优于组织S100P阳性患者的趋势(P=0.056)。
结直肠癌患者术前血清S100P水平显著高于正常人(P=7.4x10~(-9))。血清S100P诊断结直肠癌的敏感度为38.2%,相对于正常人的特异度为91.9%,联合血清CEA检测在结直肠癌患者中的阳性率可达64.4%。结直肠癌患者血清S100P水平有随肿瘤分期逐渐升高的趋势(P=0.050),其阳性率分别为Ⅰ期25.0%、Ⅱ期30.8%、Ⅲ期44.4%、Ⅳ期54.5%。术前血清S100P水平是结直肠癌患者长期生存的独立影响因素(P=0.023)。术前血清S100P阳性的结直肠癌患者的5年生存率为52.3%,而术前血清S100P阴性患者的5年生存率为81.4%(P=0.005)。在调整了临床分期的影响后,术前血清S100P升高的结直肠癌患者死亡的风险是血清S100P正常者的3.6倍。
实验结论
S100P蛋白与mRNA在结直肠癌组织中的表达显著高于配对的正常结直肠组织,S100P蛋白的表达与肿瘤的原发部位显著相关,并与患者的生存时间呈负相关趋势。S100P基因启动子区的甲基化状态与基因表达密切相关,可能在一定程度上参与调控了S100P基因的表达。结直肠癌患者术前血清S100P水平显著高于健康正常人群,并与生存时间显著相关,其水平升高提示患者预后不良。与血清CEA联合检测可提高诊断结直肠癌的敏感性。
Background:Colorectal cancer(CRC) is one of the most common types of malignant tumors worldwide.In China,CRC is the 4th leading cause of cancer-related mortality.Although great advances have been made in the diagnosis and treatment of this cancer,the survival rate of CRC patients is not improved profoundly.It has important clinical significance to put insights into the molecular mechanism of CRC and to search for the ideal markers for the early diagnosis and prognosis.In recent years,researchers has paid close attention to S100P,which has abnormal expression in many tumors and may contribute to the growth、infiltration and metastasis of tumor cells.The expression of S100P is related to the diagnosis or prognosis in some tumors.It has not been identified,however,the clinical value of the high expression of SIOOP in CRC.
Objective:To identify the clinical significance of S100P high expression in CRC tissue,and to investigate Epigenetic mechanisms of S100P expression. Moreover,the serum level of S100P in CRC and its clinical value is to be studied.
Methods:The postoperative tumor tissue samples and their paired normal colorectal tissue from 96 patients and preoperative serum specimens from 76 patients with sporadic CRC in our hospital were collected from July 2003 to July 2006.The clinical pathologic data of these patients were integrated,with the follow-up period of 30 to 65 months.
Western blot and real-time quantitative reverse-transcription PCR were performed for detecting the expression of S100P protein and mRNA in CRC tissue and in colorectal cancer cell lines.The data of the expression of S100P protein and mRNA were analyzed and correlated with the clinical pathologic information.
The correlation of S100P promoter region methylation and S100P gene expression was identified by Bisulphite Sequencing PCR(BSP).The method of fluorescence real time Quantitative Methylation Specific PCR(QMSP) was set up to detect the methylation state of S100P promoter region in CRC tissue and in colorectal cancer cell lines.The date from BSP and QMSP were then correlated with the S100P gene expression and clinical data.
Enzyme linked immunosorbent assay(ELISA) was used for detecting the serum level of S100P in patients with CRC and normal controls.The results were correlated with the clinical data to evaluate the diagnosis and prognosis value of the preoperative serum S100P level in patients with CRC.
Results:Of 96 patients with sporadic CRC involved in this study,61 were males and 35 were females,including 29 right hemicolon cancers,17 left hemicolon cancers and 50 rectal cancers.The average age was 62.4±1.2 years.63.0%(51/81) of CRC tissue express S100P protein,significantly higher than the paired control group(4.9%,P=8.13×10~(-15)).The expression of S100P mRNA in CRC tissue is also significantly higher than the paired normal group(P=0.005).The methylation state of S100P promoter region detected by BSP was strikingly correlated with the expression of S100P mRNA(P=0.002, 0.039,respectively) in colorectal cancer cell lines and tissue.A similar result was obtained through fluorescence real time QMSP in colorectal cancer cell lines and tissue(P=0.001,5.0×10~(-6),respectively).
The expression of S100P protein in CRC tissue has significant correlation with the primary cancer location.The expressing rate of S100P protein in CRC was 42.3%for right hemicolon,61.5%for left hemicolon,and 76.2%for rectum. The similar relation was not shown between the expression of S100P protein and the clinical stage.However there was no notable correlation between the expression of S100P mRNA and the clinical features of CRC such as primary cancer location and clinical stage.The quantitation of the methylation state of S100P promoter region was significantly higher in rectal cancer than in colon cancer(P=0.007),which also had a gradual downward trend according to the decrease of the tumor differentiation degree(P=0.098).In the CRC patients from stageⅠto stageⅢ,a tendency was shown that the prognosis of patients with S100P protein expression was better than that without expression(P= 0.056).
The preoperative serum level of S100P in CRC patients is significantly higher than normal controls.The sensitivity of serum S100P level for diagnosis of CRC was 38.2%and the specificity was 91.9%compared with the healthy people.Combined test of serum S100P and CEA in CRC had a positive rate up to 64.4%.The preoperative serum S100P level in CRC patients had a tendency to increase as the cancer clinical stage progressing(P=0.050).The positive rate of serum S100P in each stage of CRC was stageⅠ25.0%,stageⅡ30.8%,stageⅢ44.4%and stageⅣ54.5%.The preoperative serum level of S100P was an independent factor of long - term survival(P=0.023) in CRC patients.The 5-year cumulative survival rate of patients with a high preoperative serum S100P level was 52.3%,and the 5-year cumulative survival rate of patients with a normal serum S100P level was 81.4%(P=0.005). If adjusted the influence of clinical stage,the CRC patients with elevated preoperative serum S100P had a 3.6 times increase in the risk of death comparing with those with normal serum S100P levels.
Conclusions:The expression of S100P protein and mRNA in CRC tissue is significantly higher than the paired normal colorectal tissue.The expression of S100P protein is notably correlated with the primary cancer locations,and also has a negative correlation with survival of CRC patients.In some degree,the methylation state of S100P promoter region may regulate the expression of S100P.The preoperative serum S100P level in CRC patients is significantly higher than that in normal controls.Preoperative elevated serum S100P level correlates with a poor prognosis in CRC patients.Combined test of serum S100P and CEA can increase the sensitivity of diagnosis in CRC.
引文
1.Garcia M JA,Ward EM,Center MM,et al:Global Cancer Facts & Figures 2007.Atlanta,GA:American Cancer Society 2007.
2.American Cancer Society.Cancer Facts & Figures 2009.Atlanta:American Cancer Society 2009.
3.Sung JJ,Lau JY,Goh KL,et al:Increasing incidence of colorectal cancer in Asia:implications for screening.Lancet Oncol 2005,6(11):871-876.
4.Song F,He M,Li H,et al:A cancer incidence survey in Tianjin:the third largest city in China-between 1981 and 2000.Cancer Causes Control 2008,19(5):443-450.
5.Lu JB,Sun XB,Dai DX,et al:Epidemiology of gastroenterologic cancer in Henan Province,China.World J Gastroenterol 2003,9(11):2400-2403.
6.Sung JJ,Choi SY,Chan FK,et al:Obstacles to colorectal cancer screening in Chinese:a study based on the health belief model.Am J Gastroenterol 2008,103(4):974-981.
7.Yang L,Parkin DM,Li LD,et al:Estimation and projection of the national profile of cancer mortality in China:1991-2005.Br J Cancer 2004,90(11):2157-2166.
8.You WC,Jin F,Devesa S,et al:Rapid increase in colorectal cancer rates in urban Shanghai,1972-97,in relation to dietary changes.J Cancer Epidemiol Prev 2002,7(3):143-146.
9.Chen CJ,You SL,Lin LH,et al:Cancer epidemiology and control in Taiwan:a brief review.Jpn J Clin Oncol 2002,32 Suppl:S66-81.
10.American Cancer Society.Colorectal Cancer Facts & Figures 2008-2010.Atlanta:American Cancer Society 2008.
11.Edwards BK,Brown ML,Wingo PA,et al:Annual report to the nation on the status of cancer,1975-2002,featuring population-based trends in cancer treatment.J Natl Cancer Inst 2005,97(19):1407-1427.
12.Ciccolallo L,Capocaccia R,Coleman MP,et al:Survival differences between European and US patients with colorectal cancer:role of stage at diagnosis and surgery.Gut 2005,54(2):268-273.
13.Koltzscher M,Neumann C,Konig S,et al:Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.Mol Biol Cell 2003,14(6):2372-2384.
14.Filipek A,Jastrzebska B,Nowotny M,et al:CacyBP/SIP,a calcyclin and Siah-1-interacting protein,binds EF-hand proteins of the S100 family.J Biol Chem 2002,277(32):28848-28852.
15.Sato N,Hitomi J:S100P expression in human esophageal epithelial cells:Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation.Anat Rec 2002,267(1):60-69.
16.Arumugam T,Simeone DM,Schmidt AM,et al:S100P stimulates cell proliferation and survival via receptor for activated glycation end products(RAGE).J Biol Chem 2004,279(7):5059-5065.
17.Parkkila S,Pan PW,Ward A,et al:The calcium-binding protein S100P in normal and malignant human tissues.BMC Clin Pathol 2008,8:2.
18.Dowen SE,Cmogorac-Jurcevic T,Gangeswaran R,et al:Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.Am J Pathol 2005,166(1):81-92.
19.Mousses S,Bubendorf L,Wagner U,et al:Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays.Cancer Res 2002,62(5):1256-1260.
20.Schor AP,Carvalho FM,Kemp C,et al:S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast.Oncol Rep 2006,15(1):3-6.
21.Bartling B,Rehbein G,Schmitt WD,et al:S100A2-S100P expression profile and diagnosis of non-small cell lung carcinoma:impairment by advanced tumour stages and neoadjuvant chemotherapy.Eur J Cancer 2007,43(13):1935-1943.
22.Gao JH,He ZJ,Wang Q,et al:Low expression of S100P associated with paclitaxel resistance in ovarian cancer cell line.Chin Med J(Engl) 2008,121(16):1563-1568.
23.Bray JD,Jelinsky S,Ghatge R,et al:Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells.J Steroid Biochem Mol Bio12005,97(4):328-341.
24.Hamada S,Satoh K,Hirota M,et al:Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines.Cancer Sci 2009,100(1 ):103-110.
25.Sato N,Fukushima N,Matsubayashi H,et al:Identification of maspin and S100P as novel hypomethylation targets in.pancreatic cancer using global gene expression profiling.Oncogene 2004,23(8):1531-1538.
26.Wang Q,Williamson M,Bott S,et al:Hypomethylation of WNTSA,CRIP1 and S100P in prostate cancer.Oncogene 2007,26(45):6560-6565.
27.Rehbein G,Simm A,Hofrnann HS,et al:Molecular regulation of S100P in human lung adenocarcinomas.Int J Mol Med 2008,22(1):69-77.
28.Birkenkamp-Demtroder K,Olesen SH,Sorensen FB,et al:Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid.Gut 2005,54(3):374-384.
29.Fuentes MK,Nigavekar SS,Arumugam T,et al:RAGE activation by S100P in colon cancer stimulates growth,migration,and cell signaling pathways.Dis Colon Rectum 2007,50(8):1230-1240.
30.Lynch HT,de la Chapelle A:Hereditary colorectal cancer.N Engl J Med 2003,348(10):919-932.
31.柳川:蛋白质的提取和溶解.见:汪家政,范明,主编.蛋白质技术手册。第1版.北京:科学出版社2000:20-29.
32.陈谦:蛋白质浓度测定:Bradford 检测法.汪家政。范明,主编.蛋白质技术手册,第1版.北京:科学出版社2000:42-46.
33.Schagger H,von Jagow G:Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa.Anal Biochem 1987,166(2):368-379.
34.穆援越:免疫印迹.见:汪家政,范明,主编.蛋白质技术手册.第一版.北京:科学出版社2000:166-188.
35.孙淑芬,马福成,李江,等:苏木精.伊红染色方法.见:王伯法,李玉松,黄高异。等,主编.病理学技术,第1版.北京:人民卫生出版社2000:128-134.
36.Feil R,Charlton J,Bird AP,et al:Methylation analysis on individual chromosomes:improved protocol for bisulphite genomic sequencing.Nucleic Acids Res 1994,22(4):695-696.
37.柳川,译:低熔点琼脂糖凝胶中DNA的回收:有机溶剂提取.见:Sambrook J,Russell DW,著:黄培堂,等,译.分子克隆实验指南,第3版.北京:科学出版社2002:408-411.
38.Usadel H,Brabender J,Danenberg KD,et al:Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue,serum,and plasma DNA of patients with lung cancer.Cancer Res 2002,62(2):371-375.
39.Reddy AN,Jiang WW,Kim M,et al:Death-associated protein kinase promoter hypermethylation in normal human lymphocytes.Cancer Res 2003,63(22):7694-7698.
40.Chan MW,Chu ES,To KF,et al:Quantitative detection of methylated SOCS-1,a tumor suppressor gene,by a modified protocol of quantitative real time methylation-specific PCR using SYBR green and its use in early gastric cancer detection.Biotechnol Lett 2004,26(16):1289-1293.
41.Lenz H J:First Amsterdam,then Bethesda,now Melbourne? J Clin Oncol 2005,23(27):6445-6449.
42.Compton CC,Greene FL:The staging of colorectal cancer:2004 and beyond.CA Cancer J Clin 2004,54(6):295-308.
43.lacopetta B:Are there two sides to colorectal cancer?.Int J Cancer 2002,101(5):403-408.
44.张渊智,武子涛,李世荣:原发性结直肠癌594例的临床病理与遗传易感性.世界华人消化杂志2004.12(8):1809-1813.
45.Ekeblad S,Lejonklou MH,Grimfjjard P,et al:Co-expression of ghrelin and its receptor in pancreatic endocrine tumours.Clin Endocrinol(Oxf) 2007,66(1):115-122.
46.Becker T,Gerke V,Kube E,et al:S100P,a novel Ca(2+)-binding protein from human placenta,cDNA cloning,recombinant protein expression and Ca2+binding properties.Eur J Biochem 1992,207(2):541-547.
47.Schafer BW,Wicki R,Engelkamp D,et al:Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome lq21:rationale for a new nomenclature of the S100 calcium-binding protein family.Genomics 1995,25(3):638-643.
48.Ohuchida K,Mizumoto K,Egami T,et al:S100P is an early developmental marker of pancreatic carcinogenesis.Clin Cancer Res 2006,12(18):5411-5416.
49.Arumugam T,Simeone DM,Van Golen K,et al:S100P promotes pancreatic cancer growth,survival,and invasion.Clin Cancer Res 2005,11(15):5356-5364.
50.Basu GD,Azorsa DO,Kiefer JA,et al:Functional evidence implicating S100P in prostate cancer progression.Int J Cancer 2008,123(2):330-339.
51.Wang G,Platt-Higgins A,Carroll J,et al:Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients.Cancer Res 2006,66(2):1199-1207.
52.Diederichs S,Bulk E,Steffen B,et al:S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.Cancer Res 2004,64(16):5564-5569.
53.Surowiak P,Maciejczyk A,Materna V,et al:Unfavourable prognostic significance of S100P expression in ovarian cancers.Histopathology 2007,51(1):125-128.
54.He Z,Gao J,Wang Q,et al:S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3.Oncol Rep 2008,20(2):325-332.
55.Glebov OK,Rodriguez LM,Nakahara K,et al:Distinguishing right from left colon by the pattern of gene expression.Cancer Epidemiol Biomarkers Prev 2003,12(8):755-762.
56.Crawford NP,Colliver DW,Galandiuk S:Tumor markers and colorectal cancer:utility in management.J Surg Oncol 2003,84(4):239-248.
57.Pokorny RM,Hunt L,Galandiuk S:What's new with tumor markers for colorectal cancer?Dig Surg 2000,17(3):209-215.
58.Chapman MA,Buckley D,Henson DB,et al:Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.Br J Cancer 1998,78(10):1346-1349.
59.Guerreiro Da Silva ID,Hu YF,Russo IH,et al:S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.Int J Oncol 2000,16(2):231-240.
60.Bird A:DNA methylation patterns and epigenetic memory.Genes Dev 2002,16(1):6-21.
61.Weber M,Schubeler D:Genomic patterns of DNA methylation:targets and function of an epigenetic mark.Curr Opin Cell Biol 2007,19(3):273-280.
62.Weber M,Hellmann I,Stadler MB,et al:Distribution,silencing potential and evolutionary impact of promoter DNA methylation in the human genome.Nat Genet 2007,39(4):457-466.
63.Hatada I,Fukasawa M,Kimura M,et al:Genome-wide profiling of promoter methylation in human.Oncogene 2006,25(21):3059-3064.
64.Rouhi A,Gagnier L,Takei F,et al:Evidence for epigenetic maintenance of Ly49a monoallelic gene expression.J Immunol 2006,176(5):2991-2999.
65.Fujii G,Nakamura Y,Tsukamoto D,et al:CpG methylation at the USF-binding site is important for the liver-specific transcription of the chipmunk HP-27 gene.Biochem J 2006,395(1):203-209.
66.Bock C,Walter J,Paulsen M,et al:Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping.Nucleic Acids Res 2008,36(10):e55.
67.Herman JG,Graff JR,Myohanen S,et al:Methylation-specific PCR:a novel PCR assay for methylation status of CpG islands.Proc Natl Acad Sci U S A 1996,93(18):9821-9826.
68.Sulewska A,Niklinska W,Kozlowski M,et al:Detection of DNA methyiation in eucaryotic cells.Folia Histochem Cytobiol 2007,45(4):315-324.
69.Cottrell SE:Molecular diagnostic applications of DNA methyiation technology.Clin Biochem 2004,37(7):595-604.
70.Hoque MO,Topaloglu O,Begum S,et al:Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects.J Clin Oncol 2005,23(27):6569-6575.
71.Roupret M,Hupertan V,Yates DR,et al:Molecular detection of localized prostate cancer-using quantitative methylation-specific PCR on urinary cells obtained following prostate massage.Clin Cancer Res 2007,13(6):1720-1725.
72.Dworkin AM,Huang TH,Toland AE:Epigenetic alterations in the breast:Implications for breast cancer detection,prognosis and treatment.Semin Cancer Biol 2009,19(3):165-171.
73.Kamiyama H,Noda H,Takata O,et al:Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer.J Surg Oncol 2009.
74.Kim DS,Kim MJ,Lee JY,et al:Epigenetic inactivation of checkpoint kinase 2 gene in non-small cell lung cancer and its relationship with clinicopathological features.Lung Cancer 2009.
75.Chen SP,Chiu SC,Wu CC,et al:The association of methyiation in the promoter of APC and MGMT and the prognosis of Taiwanese CRC patients.Genet Test Mol Biomarkers 2009,13(1):67-71.
1.Marenholz I,Heizmann CW,Fritz G:S100 proteins in mouse and man:from evolution to function and pathology(including an update of the nomenclature).Biochem Biophys Res Commun 2004,322(4):1111-1122.
2.Foell D,Frosch M,Sorg C et al:Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation.Clin Chim Acta 2004,344(1-2):37-51.
3.Gribenko A,Lopez MM,Richardson JM,3rd et al:Cloning,overexpression,purification,and spectroscopic characterization of human SLOOP.Protein Sci 1998,7(1):211-215.
4.Donato R:S 100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol 2001,33(7):637-668.
5.Hofinann MA,Drury S,Fu C et al:RAGE mediates a novel proinflammatory axis:a central cell surface receptor for S100/calgranulin polypeptides.Cell 1999,97(7):889-901.
6.Schmidt AM,Yan SD,Yah SF et al:The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses.J Clin lnvest 2001,108(7):949-955.
7.Becker T,Gerke V,Kube E et al:SLOOP,a novel Ca(2+)-binding protein from human placenta,cDNA cloning,recombinant protein expression and Ca2+ binding properties.Eur J Biochem 1992,207(2):541-547.
8.Schafer BW,Wicki R,Engelkamp D et al:Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21:rationale for a new nomenclature of the S 100 calcium-binding protein family.Genomics 1995,25(3):638-643.
9.Zhang H,Wang G;Ding Yet al:The crystal structure at 2A resolution of the Ca2+-binding protein SLOOP.JMol Bio12003,325(4):785-794.
10.Emberley ED,Murphy LC,Watson PH:S100 proteins and their influence on pro-survival pathways in cancer.Biochem Cell Biol 2004,82(4):508-515.
11.Jin G,Wang S,Hu X et al:Characterization of the tissue-specific expression of the s100P gene which encodes an EF-hand Ca2+-binding protein.Mol Biol Rep 2003,30(4):243-248.
12.Sato N,Hitomi J:S1OOP expression in human esophageal epithelial cells:Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation.Anat Rec 2002,267(1):60-69.
13.Guerreiro Da Silva ID,Hu YF,Russo IH et al:S1OOP calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.lnt J Onco12000,16(2):231-240.
14.Dhanasekaran SM,Dash A,Yu Jet al:Molecular profiling of human prostate tissues:insights into gene expression patterns of prostate development during puberty.FASEB J 2005,19(2):243-245.
15.Crnogorac-Jurcevic T,Missiaglia E,Blaveri E et al.Molecular alterations in pancreatic carcinoma:expression profiling shows that dysregulated expression of S100 genes is highly prevalent.J Pathol 2003,201(1):63-74.
16.Logsdon CD,Simeone DM,Binkley C et al.Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer.Cancer Res 2003,63(10):2649-2657.
17.Parkkila S,Pan PW,Ward A et al.The calcium-binding protein S100P in normal and malignant human tissues.BMC Clin Pathol 2008,8:2.
18.Birkenkamp-Demtroder K,Olesen SH,Sorensen FB et al.Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid.Gut 2005,54(3):374-384.
19.Glebov OK,Rodriguez LM,Nakahara K et al.Distinguishing right from left colon by the pattern of gene expression.Cancer Epidemiol Biomarkers Prev 2003,12(8):755-762.
20.Mousses S,Bubendorf L,Wagner U et al.Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays.Cancer Res 2002,62(5):1256-1260.
21.Dowen SE,Crnogorac-Jurcevic T,Gangeswaran R et al.Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.Am J Pathol 2005,166(1):81-92.
22.Iacobuzio-Donahue CA,Maitra A,Shen-Ong GL et al.Discovery of novel tumor markers of pancreatic cancer using global gene expression technology.Am J Pathol 2002,160(4):1239-1249.
23.Koltzscher M,Neumann C,Konig S et al.Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.Mol Biol Cell 2003,14(6):2372-2384.
24.Filipek A,Jastrzebska B,Nowotny M et al.CacyBP/SIP,a calcyclin and Siah-1-interacting protein,binds EF-hand proteins of the S1 00 family.J Biol Chem 2002,277(32):28848-28852.
25.Arumugam T,Simeone DM,Schmidt AM et al..S100P stimulates cell proliferation and survival via receptor for activated glycation end products(RAGE).J Biol Chem 2004,279(7):5059-5065.
26.Terris B,Blaveri E,Crnogorac-Jurcevic T et al.Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas.Am J Pathol 2002,160(5):1745-1754.
27.Iacobuzio-Donahue CA,Ashfaq R,Maitra A et al.Highly expressed genes in pancreatic ductal adenocarcinomas:a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies.Cancer Res 2003,63(24):8614-8622.
28.Iacobuzio-Donahue CA,Maitra A,Olsen M et al.Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays.Am J Pathol 2003,162(4):1151-1162.
29.Sato N,Fukushima N,Matsubayashi H et al.Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling.Oncogene 2004,23(8):1531-1538.
30.Nakamura T,Furukawa Y,Nakagawa H et al.Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection.Oncogene 2004,23(13):2385-2400.
31.Missiaglia E,Blaveri E,Terris B et al.Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis.Int J Cancer 2004,112(1):100-112.
32.Fukushima N,Sato N,Prasad N et al.Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays.Oncogene 2004,23(56):9042-9051.
33.Ohuchida K,Mizumoto K,Egami T et al.S100P is an early developmental marker of pancreatic carcinogenesis.Clin Cancer Res 2006,12(18):5411-5416.
34.Lin F,Shi J,Liu H et al.Diagnostic utility of S100P and von Hippel-Lindau gene product(pVHL) in pancreatic adenocarcinoma-with implication of their roles in early tumorigenesis.Am J Surg Pathol 2008,32(1):78-91.
35.Deng H,Shi J,Wilkerson M et al:Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens.Am J Clin Pathol 2008,129(1):81-88.
36.Arumugam T,Simeone DM,Van Golen K et al.S100P promotes pancreatic cancer growth,survival,and invasion.Clin Cancer Res 2005,11(15):5356-5364.
37.Arumugam T,Ramachandran V,Logsdon CD:Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth and invasion in mouse models.J Natl Cancer Inst 2006,98(24):1806-1818.
38.Whiteman HJ,Weeks ME,Dowen SE et al.The role of S100P in the invasion of pancreatic cancer cells is mediated through cytoskeletal changes and regulation of cathepsin D.Cancer Res 2007,67(18):8633-8642.
39.Hamada S,Satoh K,Hirota M et al.Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines.Cancer Sci 2009,100(1):103-110.
40.Basu GD,Azorsa DO,Kiefer JA et al.Functional evidence implicating S100P in prostate cancer progression.Int J Cancer 2008,123(2):330-339.
41.Higgins JP,Kaygusuz G,Wang L et al.Placental S100(S100P) and GATA3:markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray.Am J Surg Pathol 2007,31(5):673-680.
42.Amler LC,Agus DB,LeDuc C et al.Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1.Cancer Res 2000,60(21):6134-6141.
43.Averboukh L,Liang P,Kantoff PW et al.Regulation of S100P expression by androgen.Prostate 1996,29(6):350-355.
44.Hammacher A,Thompson EW,Williams ED:Interleukin-6 is a potent inducer of S100P,which is up-regulated in androgen-refractory and metastatic prostate cancer.Int J Biochem Cell Biol 2005,37(2):442-450.
45.Wang Q,Williamson M,Bott S et al.Hypomethylation of WNT5A,CPIP1 and S100P in prostate cancer.Oncogene 2007,26(45):6560-6565.
46.Schor AP,Carvalho FM,Kemp C et al:S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast.Oncol Rep 2006,15(1):3-6.
47.Wang G,Platt-Higgins A,Carroll J et al.Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients.Cancer Res 2006,66(2):1199-1207.
48.Beissel B,Silva ID,Pesquero JB et al.S-phase reduction in T47D human breast cancer epithelial cells induced by an S100P antisense-retroviral construct.Oncol Rep 2007,17(3):611-615.
49.Milde-Langosch K,Janke S,Wagner Ⅰ et al.Role of Fra-2 in breast cancer,influence on tumor cell invasion and-motilityr.Breast Cancer Res Treat 2008,107(3):337-347.
50.Bray JD,Jelinsky S,Ghatge R et al.Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells.J Steroid Biochem Mol Biol 2005,97(4):328-341.
51.Bigelow RL,Williams BJ,Carroll JL et al.TIMP-1 overexpression promotes tumorigenesis of MDA-MB-231 breast cancer cells and alters expression of a subset of cancer promoting genes in vivo distinct from those observed in vitro.Breast Cancer Res Treat 2008.
52.Mountain CF:Revisions in the International System for Staging Lung Cancer.Chest 1997,111(6):1710-1717.
53.Diederichs S,Bulk E,Steffen B et al.S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.Cancer Res 2004,64(16):5564-5569.
54.Bulk E,Hascher A,Liersch R et al.Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice.Cancer Res 2008,68(6):1896-1904.
55.Bartling B,Rehbein G,Schmitt WD et al.S100A2-S100P expression profile and diagnosis of non-small cell lung carcinoma:impairment by advanced tumour stages and neoadjuvant chemotherapy.Eur J Cancer 2007,43(13):1935-1943.
56.Rehbein G,Simm A,Hofmann HS et al.Molecular regulation of S100P in human lung adenocarcinomas.Int J Mol Med 2008,22(l):69-77.
57.Surowiak P,Maciejczyk A,Materna V et al.Unfavourable prognostic significance of S100P expression in ovarian cancers.Histopathology 2007,51(1):125-128.
58.Chao A,Wang TH,Lai CH:Overview of microarray analysis of gene expression and its applications to cervical cancer investigation.Taiwan J Obstet Gynecol 2007,46(4):363-373.
59.Gao JH,He ZJ,Wang Q et al.Low expression of S100P associated with paclitaxel resistance in ovarian cancer cell line.Chin Med J(Engl) 2008,121(16):1563-1568.
60.He Z,Gao J,Wang Q et a;.S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3.Oncol Rep 2008,20(2):325-332.
61.Fuentes MK,Nigavekar SS,Arumugam T et al:RAGE activation by S100P in colon cancer stimulates growth,migration,and cell signaling pathways.Dis Colon Rectum 2007,50(8):1230-1240.
62.Bertram J,Palmer K,Hiddemann W et al.Elevated expression of S100P,CAPL and MAGE 3 in doxorubicin-resistant cell lines:comparison of mRNA differential display reverse transcription-polymerase chain reaction and subtractive suppressive hybridization for the analysis of differential gene expression.Anticancer Drugs 1998,9(4):311-317.
63.Tang H,Liu YJ,Liu M et al:Establishment and gene analysis of an oxaliplatin-resistant colon cancer cell line THC8307/L-OHP.Anticancer Drugs 2007,18(6):633-639.
64.Sawyers CL:The cancer biomarker problem.Nature 2008,452(7187):548-552.
65.Battling B,Hofmann HS,Weigle B et al:Down-regulation of the receptor for advanced glycation end-products(RAGE) supports non-small cell lung carcinoma.Carcinogenesis 2005,26(2):293-301.
66.Austermann J,Nazmi AR,Muller-Tidow-Cet al:Characterization of the Ca2+ -regulated ezrin-S100P interaction and its role in rumor cell migration,J Biol Chem 2008,283(43):29331-29340.
2.American Cancer Society.Cancer Facts & Figures 2009.Atlanta:American Cancer Society 2009.
3.Sung JJ,Lau JY,Goh KL,et al:Increasing incidence of colorectal cancer in Asia:implications for screening.Lancet Oncol 2005,6(11):871-876.
4.Song F,He M,Li H,et al:A cancer incidence survey in Tianjin:the third largest city in China-between 1981 and 2000.Cancer Causes Control 2008,19(5):443-450.
5.Lu JB,Sun XB,Dai DX,et al:Epidemiology of gastroenterologic cancer in Henan Province,China.World J Gastroenterol 2003,9(11):2400-2403.
6.Sung JJ,Choi SY,Chan FK,et al:Obstacles to colorectal cancer screening in Chinese:a study based on the health belief model.Am J Gastroenterol 2008,103(4):974-981.
7.Yang L,Parkin DM,Li LD,et al:Estimation and projection of the national profile of cancer mortality in China:1991-2005.Br J Cancer 2004,90(11):2157-2166.
8.You WC,Jin F,Devesa S,et al:Rapid increase in colorectal cancer rates in urban Shanghai,1972-97,in relation to dietary changes.J Cancer Epidemiol Prev 2002,7(3):143-146.
9.Chen CJ,You SL,Lin LH,et al:Cancer epidemiology and control in Taiwan:a brief review.Jpn J Clin Oncol 2002,32 Suppl:S66-81.
10.American Cancer Society.Colorectal Cancer Facts & Figures 2008-2010.Atlanta:American Cancer Society 2008.
11.Edwards BK,Brown ML,Wingo PA,et al:Annual report to the nation on the status of cancer,1975-2002,featuring population-based trends in cancer treatment.J Natl Cancer Inst 2005,97(19):1407-1427.
12.Ciccolallo L,Capocaccia R,Coleman MP,et al:Survival differences between European and US patients with colorectal cancer:role of stage at diagnosis and surgery.Gut 2005,54(2):268-273.
13.Koltzscher M,Neumann C,Konig S,et al:Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.Mol Biol Cell 2003,14(6):2372-2384.
14.Filipek A,Jastrzebska B,Nowotny M,et al:CacyBP/SIP,a calcyclin and Siah-1-interacting protein,binds EF-hand proteins of the S100 family.J Biol Chem 2002,277(32):28848-28852.
15.Sato N,Hitomi J:S100P expression in human esophageal epithelial cells:Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation.Anat Rec 2002,267(1):60-69.
16.Arumugam T,Simeone DM,Schmidt AM,et al:S100P stimulates cell proliferation and survival via receptor for activated glycation end products(RAGE).J Biol Chem 2004,279(7):5059-5065.
17.Parkkila S,Pan PW,Ward A,et al:The calcium-binding protein S100P in normal and malignant human tissues.BMC Clin Pathol 2008,8:2.
18.Dowen SE,Cmogorac-Jurcevic T,Gangeswaran R,et al:Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.Am J Pathol 2005,166(1):81-92.
19.Mousses S,Bubendorf L,Wagner U,et al:Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays.Cancer Res 2002,62(5):1256-1260.
20.Schor AP,Carvalho FM,Kemp C,et al:S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast.Oncol Rep 2006,15(1):3-6.
21.Bartling B,Rehbein G,Schmitt WD,et al:S100A2-S100P expression profile and diagnosis of non-small cell lung carcinoma:impairment by advanced tumour stages and neoadjuvant chemotherapy.Eur J Cancer 2007,43(13):1935-1943.
22.Gao JH,He ZJ,Wang Q,et al:Low expression of S100P associated with paclitaxel resistance in ovarian cancer cell line.Chin Med J(Engl) 2008,121(16):1563-1568.
23.Bray JD,Jelinsky S,Ghatge R,et al:Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells.J Steroid Biochem Mol Bio12005,97(4):328-341.
24.Hamada S,Satoh K,Hirota M,et al:Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines.Cancer Sci 2009,100(1 ):103-110.
25.Sato N,Fukushima N,Matsubayashi H,et al:Identification of maspin and S100P as novel hypomethylation targets in.pancreatic cancer using global gene expression profiling.Oncogene 2004,23(8):1531-1538.
26.Wang Q,Williamson M,Bott S,et al:Hypomethylation of WNTSA,CRIP1 and S100P in prostate cancer.Oncogene 2007,26(45):6560-6565.
27.Rehbein G,Simm A,Hofrnann HS,et al:Molecular regulation of S100P in human lung adenocarcinomas.Int J Mol Med 2008,22(1):69-77.
28.Birkenkamp-Demtroder K,Olesen SH,Sorensen FB,et al:Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid.Gut 2005,54(3):374-384.
29.Fuentes MK,Nigavekar SS,Arumugam T,et al:RAGE activation by S100P in colon cancer stimulates growth,migration,and cell signaling pathways.Dis Colon Rectum 2007,50(8):1230-1240.
30.Lynch HT,de la Chapelle A:Hereditary colorectal cancer.N Engl J Med 2003,348(10):919-932.
31.柳川:蛋白质的提取和溶解.见:汪家政,范明,主编.蛋白质技术手册。第1版.北京:科学出版社2000:20-29.
32.陈谦:蛋白质浓度测定:Bradford 检测法.汪家政。范明,主编.蛋白质技术手册,第1版.北京:科学出版社2000:42-46.
33.Schagger H,von Jagow G:Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa.Anal Biochem 1987,166(2):368-379.
34.穆援越:免疫印迹.见:汪家政,范明,主编.蛋白质技术手册.第一版.北京:科学出版社2000:166-188.
35.孙淑芬,马福成,李江,等:苏木精.伊红染色方法.见:王伯法,李玉松,黄高异。等,主编.病理学技术,第1版.北京:人民卫生出版社2000:128-134.
36.Feil R,Charlton J,Bird AP,et al:Methylation analysis on individual chromosomes:improved protocol for bisulphite genomic sequencing.Nucleic Acids Res 1994,22(4):695-696.
37.柳川,译:低熔点琼脂糖凝胶中DNA的回收:有机溶剂提取.见:Sambrook J,Russell DW,著:黄培堂,等,译.分子克隆实验指南,第3版.北京:科学出版社2002:408-411.
38.Usadel H,Brabender J,Danenberg KD,et al:Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue,serum,and plasma DNA of patients with lung cancer.Cancer Res 2002,62(2):371-375.
39.Reddy AN,Jiang WW,Kim M,et al:Death-associated protein kinase promoter hypermethylation in normal human lymphocytes.Cancer Res 2003,63(22):7694-7698.
40.Chan MW,Chu ES,To KF,et al:Quantitative detection of methylated SOCS-1,a tumor suppressor gene,by a modified protocol of quantitative real time methylation-specific PCR using SYBR green and its use in early gastric cancer detection.Biotechnol Lett 2004,26(16):1289-1293.
41.Lenz H J:First Amsterdam,then Bethesda,now Melbourne? J Clin Oncol 2005,23(27):6445-6449.
42.Compton CC,Greene FL:The staging of colorectal cancer:2004 and beyond.CA Cancer J Clin 2004,54(6):295-308.
43.lacopetta B:Are there two sides to colorectal cancer?.Int J Cancer 2002,101(5):403-408.
44.张渊智,武子涛,李世荣:原发性结直肠癌594例的临床病理与遗传易感性.世界华人消化杂志2004.12(8):1809-1813.
45.Ekeblad S,Lejonklou MH,Grimfjjard P,et al:Co-expression of ghrelin and its receptor in pancreatic endocrine tumours.Clin Endocrinol(Oxf) 2007,66(1):115-122.
46.Becker T,Gerke V,Kube E,et al:S100P,a novel Ca(2+)-binding protein from human placenta,cDNA cloning,recombinant protein expression and Ca2+binding properties.Eur J Biochem 1992,207(2):541-547.
47.Schafer BW,Wicki R,Engelkamp D,et al:Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome lq21:rationale for a new nomenclature of the S100 calcium-binding protein family.Genomics 1995,25(3):638-643.
48.Ohuchida K,Mizumoto K,Egami T,et al:S100P is an early developmental marker of pancreatic carcinogenesis.Clin Cancer Res 2006,12(18):5411-5416.
49.Arumugam T,Simeone DM,Van Golen K,et al:S100P promotes pancreatic cancer growth,survival,and invasion.Clin Cancer Res 2005,11(15):5356-5364.
50.Basu GD,Azorsa DO,Kiefer JA,et al:Functional evidence implicating S100P in prostate cancer progression.Int J Cancer 2008,123(2):330-339.
51.Wang G,Platt-Higgins A,Carroll J,et al:Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients.Cancer Res 2006,66(2):1199-1207.
52.Diederichs S,Bulk E,Steffen B,et al:S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.Cancer Res 2004,64(16):5564-5569.
53.Surowiak P,Maciejczyk A,Materna V,et al:Unfavourable prognostic significance of S100P expression in ovarian cancers.Histopathology 2007,51(1):125-128.
54.He Z,Gao J,Wang Q,et al:S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3.Oncol Rep 2008,20(2):325-332.
55.Glebov OK,Rodriguez LM,Nakahara K,et al:Distinguishing right from left colon by the pattern of gene expression.Cancer Epidemiol Biomarkers Prev 2003,12(8):755-762.
56.Crawford NP,Colliver DW,Galandiuk S:Tumor markers and colorectal cancer:utility in management.J Surg Oncol 2003,84(4):239-248.
57.Pokorny RM,Hunt L,Galandiuk S:What's new with tumor markers for colorectal cancer?Dig Surg 2000,17(3):209-215.
58.Chapman MA,Buckley D,Henson DB,et al:Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.Br J Cancer 1998,78(10):1346-1349.
59.Guerreiro Da Silva ID,Hu YF,Russo IH,et al:S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.Int J Oncol 2000,16(2):231-240.
60.Bird A:DNA methylation patterns and epigenetic memory.Genes Dev 2002,16(1):6-21.
61.Weber M,Schubeler D:Genomic patterns of DNA methylation:targets and function of an epigenetic mark.Curr Opin Cell Biol 2007,19(3):273-280.
62.Weber M,Hellmann I,Stadler MB,et al:Distribution,silencing potential and evolutionary impact of promoter DNA methylation in the human genome.Nat Genet 2007,39(4):457-466.
63.Hatada I,Fukasawa M,Kimura M,et al:Genome-wide profiling of promoter methylation in human.Oncogene 2006,25(21):3059-3064.
64.Rouhi A,Gagnier L,Takei F,et al:Evidence for epigenetic maintenance of Ly49a monoallelic gene expression.J Immunol 2006,176(5):2991-2999.
65.Fujii G,Nakamura Y,Tsukamoto D,et al:CpG methylation at the USF-binding site is important for the liver-specific transcription of the chipmunk HP-27 gene.Biochem J 2006,395(1):203-209.
66.Bock C,Walter J,Paulsen M,et al:Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping.Nucleic Acids Res 2008,36(10):e55.
67.Herman JG,Graff JR,Myohanen S,et al:Methylation-specific PCR:a novel PCR assay for methylation status of CpG islands.Proc Natl Acad Sci U S A 1996,93(18):9821-9826.
68.Sulewska A,Niklinska W,Kozlowski M,et al:Detection of DNA methyiation in eucaryotic cells.Folia Histochem Cytobiol 2007,45(4):315-324.
69.Cottrell SE:Molecular diagnostic applications of DNA methyiation technology.Clin Biochem 2004,37(7):595-604.
70.Hoque MO,Topaloglu O,Begum S,et al:Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects.J Clin Oncol 2005,23(27):6569-6575.
71.Roupret M,Hupertan V,Yates DR,et al:Molecular detection of localized prostate cancer-using quantitative methylation-specific PCR on urinary cells obtained following prostate massage.Clin Cancer Res 2007,13(6):1720-1725.
72.Dworkin AM,Huang TH,Toland AE:Epigenetic alterations in the breast:Implications for breast cancer detection,prognosis and treatment.Semin Cancer Biol 2009,19(3):165-171.
73.Kamiyama H,Noda H,Takata O,et al:Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer.J Surg Oncol 2009.
74.Kim DS,Kim MJ,Lee JY,et al:Epigenetic inactivation of checkpoint kinase 2 gene in non-small cell lung cancer and its relationship with clinicopathological features.Lung Cancer 2009.
75.Chen SP,Chiu SC,Wu CC,et al:The association of methyiation in the promoter of APC and MGMT and the prognosis of Taiwanese CRC patients.Genet Test Mol Biomarkers 2009,13(1):67-71.
1.Marenholz I,Heizmann CW,Fritz G:S100 proteins in mouse and man:from evolution to function and pathology(including an update of the nomenclature).Biochem Biophys Res Commun 2004,322(4):1111-1122.
2.Foell D,Frosch M,Sorg C et al:Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation.Clin Chim Acta 2004,344(1-2):37-51.
3.Gribenko A,Lopez MM,Richardson JM,3rd et al:Cloning,overexpression,purification,and spectroscopic characterization of human SLOOP.Protein Sci 1998,7(1):211-215.
4.Donato R:S 100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol 2001,33(7):637-668.
5.Hofinann MA,Drury S,Fu C et al:RAGE mediates a novel proinflammatory axis:a central cell surface receptor for S100/calgranulin polypeptides.Cell 1999,97(7):889-901.
6.Schmidt AM,Yan SD,Yah SF et al:The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses.J Clin lnvest 2001,108(7):949-955.
7.Becker T,Gerke V,Kube E et al:SLOOP,a novel Ca(2+)-binding protein from human placenta,cDNA cloning,recombinant protein expression and Ca2+ binding properties.Eur J Biochem 1992,207(2):541-547.
8.Schafer BW,Wicki R,Engelkamp D et al:Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21:rationale for a new nomenclature of the S 100 calcium-binding protein family.Genomics 1995,25(3):638-643.
9.Zhang H,Wang G;Ding Yet al:The crystal structure at 2A resolution of the Ca2+-binding protein SLOOP.JMol Bio12003,325(4):785-794.
10.Emberley ED,Murphy LC,Watson PH:S100 proteins and their influence on pro-survival pathways in cancer.Biochem Cell Biol 2004,82(4):508-515.
11.Jin G,Wang S,Hu X et al:Characterization of the tissue-specific expression of the s100P gene which encodes an EF-hand Ca2+-binding protein.Mol Biol Rep 2003,30(4):243-248.
12.Sato N,Hitomi J:S1OOP expression in human esophageal epithelial cells:Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation.Anat Rec 2002,267(1):60-69.
13.Guerreiro Da Silva ID,Hu YF,Russo IH et al:S1OOP calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.lnt J Onco12000,16(2):231-240.
14.Dhanasekaran SM,Dash A,Yu Jet al:Molecular profiling of human prostate tissues:insights into gene expression patterns of prostate development during puberty.FASEB J 2005,19(2):243-245.
15.Crnogorac-Jurcevic T,Missiaglia E,Blaveri E et al.Molecular alterations in pancreatic carcinoma:expression profiling shows that dysregulated expression of S100 genes is highly prevalent.J Pathol 2003,201(1):63-74.
16.Logsdon CD,Simeone DM,Binkley C et al.Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer.Cancer Res 2003,63(10):2649-2657.
17.Parkkila S,Pan PW,Ward A et al.The calcium-binding protein S100P in normal and malignant human tissues.BMC Clin Pathol 2008,8:2.
18.Birkenkamp-Demtroder K,Olesen SH,Sorensen FB et al.Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid.Gut 2005,54(3):374-384.
19.Glebov OK,Rodriguez LM,Nakahara K et al.Distinguishing right from left colon by the pattern of gene expression.Cancer Epidemiol Biomarkers Prev 2003,12(8):755-762.
20.Mousses S,Bubendorf L,Wagner U et al.Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays.Cancer Res 2002,62(5):1256-1260.
21.Dowen SE,Crnogorac-Jurcevic T,Gangeswaran R et al.Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.Am J Pathol 2005,166(1):81-92.
22.Iacobuzio-Donahue CA,Maitra A,Shen-Ong GL et al.Discovery of novel tumor markers of pancreatic cancer using global gene expression technology.Am J Pathol 2002,160(4):1239-1249.
23.Koltzscher M,Neumann C,Konig S et al.Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.Mol Biol Cell 2003,14(6):2372-2384.
24.Filipek A,Jastrzebska B,Nowotny M et al.CacyBP/SIP,a calcyclin and Siah-1-interacting protein,binds EF-hand proteins of the S1 00 family.J Biol Chem 2002,277(32):28848-28852.
25.Arumugam T,Simeone DM,Schmidt AM et al..S100P stimulates cell proliferation and survival via receptor for activated glycation end products(RAGE).J Biol Chem 2004,279(7):5059-5065.
26.Terris B,Blaveri E,Crnogorac-Jurcevic T et al.Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas.Am J Pathol 2002,160(5):1745-1754.
27.Iacobuzio-Donahue CA,Ashfaq R,Maitra A et al.Highly expressed genes in pancreatic ductal adenocarcinomas:a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies.Cancer Res 2003,63(24):8614-8622.
28.Iacobuzio-Donahue CA,Maitra A,Olsen M et al.Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays.Am J Pathol 2003,162(4):1151-1162.
29.Sato N,Fukushima N,Matsubayashi H et al.Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling.Oncogene 2004,23(8):1531-1538.
30.Nakamura T,Furukawa Y,Nakagawa H et al.Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection.Oncogene 2004,23(13):2385-2400.
31.Missiaglia E,Blaveri E,Terris B et al.Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis.Int J Cancer 2004,112(1):100-112.
32.Fukushima N,Sato N,Prasad N et al.Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays.Oncogene 2004,23(56):9042-9051.
33.Ohuchida K,Mizumoto K,Egami T et al.S100P is an early developmental marker of pancreatic carcinogenesis.Clin Cancer Res 2006,12(18):5411-5416.
34.Lin F,Shi J,Liu H et al.Diagnostic utility of S100P and von Hippel-Lindau gene product(pVHL) in pancreatic adenocarcinoma-with implication of their roles in early tumorigenesis.Am J Surg Pathol 2008,32(1):78-91.
35.Deng H,Shi J,Wilkerson M et al:Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens.Am J Clin Pathol 2008,129(1):81-88.
36.Arumugam T,Simeone DM,Van Golen K et al.S100P promotes pancreatic cancer growth,survival,and invasion.Clin Cancer Res 2005,11(15):5356-5364.
37.Arumugam T,Ramachandran V,Logsdon CD:Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth and invasion in mouse models.J Natl Cancer Inst 2006,98(24):1806-1818.
38.Whiteman HJ,Weeks ME,Dowen SE et al.The role of S100P in the invasion of pancreatic cancer cells is mediated through cytoskeletal changes and regulation of cathepsin D.Cancer Res 2007,67(18):8633-8642.
39.Hamada S,Satoh K,Hirota M et al.Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines.Cancer Sci 2009,100(1):103-110.
40.Basu GD,Azorsa DO,Kiefer JA et al.Functional evidence implicating S100P in prostate cancer progression.Int J Cancer 2008,123(2):330-339.
41.Higgins JP,Kaygusuz G,Wang L et al.Placental S100(S100P) and GATA3:markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray.Am J Surg Pathol 2007,31(5):673-680.
42.Amler LC,Agus DB,LeDuc C et al.Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1.Cancer Res 2000,60(21):6134-6141.
43.Averboukh L,Liang P,Kantoff PW et al.Regulation of S100P expression by androgen.Prostate 1996,29(6):350-355.
44.Hammacher A,Thompson EW,Williams ED:Interleukin-6 is a potent inducer of S100P,which is up-regulated in androgen-refractory and metastatic prostate cancer.Int J Biochem Cell Biol 2005,37(2):442-450.
45.Wang Q,Williamson M,Bott S et al.Hypomethylation of WNT5A,CPIP1 and S100P in prostate cancer.Oncogene 2007,26(45):6560-6565.
46.Schor AP,Carvalho FM,Kemp C et al:S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast.Oncol Rep 2006,15(1):3-6.
47.Wang G,Platt-Higgins A,Carroll J et al.Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients.Cancer Res 2006,66(2):1199-1207.
48.Beissel B,Silva ID,Pesquero JB et al.S-phase reduction in T47D human breast cancer epithelial cells induced by an S100P antisense-retroviral construct.Oncol Rep 2007,17(3):611-615.
49.Milde-Langosch K,Janke S,Wagner Ⅰ et al.Role of Fra-2 in breast cancer,influence on tumor cell invasion and-motilityr.Breast Cancer Res Treat 2008,107(3):337-347.
50.Bray JD,Jelinsky S,Ghatge R et al.Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells.J Steroid Biochem Mol Biol 2005,97(4):328-341.
51.Bigelow RL,Williams BJ,Carroll JL et al.TIMP-1 overexpression promotes tumorigenesis of MDA-MB-231 breast cancer cells and alters expression of a subset of cancer promoting genes in vivo distinct from those observed in vitro.Breast Cancer Res Treat 2008.
52.Mountain CF:Revisions in the International System for Staging Lung Cancer.Chest 1997,111(6):1710-1717.
53.Diederichs S,Bulk E,Steffen B et al.S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.Cancer Res 2004,64(16):5564-5569.
54.Bulk E,Hascher A,Liersch R et al.Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice.Cancer Res 2008,68(6):1896-1904.
55.Bartling B,Rehbein G,Schmitt WD et al.S100A2-S100P expression profile and diagnosis of non-small cell lung carcinoma:impairment by advanced tumour stages and neoadjuvant chemotherapy.Eur J Cancer 2007,43(13):1935-1943.
56.Rehbein G,Simm A,Hofmann HS et al.Molecular regulation of S100P in human lung adenocarcinomas.Int J Mol Med 2008,22(l):69-77.
57.Surowiak P,Maciejczyk A,Materna V et al.Unfavourable prognostic significance of S100P expression in ovarian cancers.Histopathology 2007,51(1):125-128.
58.Chao A,Wang TH,Lai CH:Overview of microarray analysis of gene expression and its applications to cervical cancer investigation.Taiwan J Obstet Gynecol 2007,46(4):363-373.
59.Gao JH,He ZJ,Wang Q et al.Low expression of S100P associated with paclitaxel resistance in ovarian cancer cell line.Chin Med J(Engl) 2008,121(16):1563-1568.
60.He Z,Gao J,Wang Q et a;.S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3.Oncol Rep 2008,20(2):325-332.
61.Fuentes MK,Nigavekar SS,Arumugam T et al:RAGE activation by S100P in colon cancer stimulates growth,migration,and cell signaling pathways.Dis Colon Rectum 2007,50(8):1230-1240.
62.Bertram J,Palmer K,Hiddemann W et al.Elevated expression of S100P,CAPL and MAGE 3 in doxorubicin-resistant cell lines:comparison of mRNA differential display reverse transcription-polymerase chain reaction and subtractive suppressive hybridization for the analysis of differential gene expression.Anticancer Drugs 1998,9(4):311-317.
63.Tang H,Liu YJ,Liu M et al:Establishment and gene analysis of an oxaliplatin-resistant colon cancer cell line THC8307/L-OHP.Anticancer Drugs 2007,18(6):633-639.
64.Sawyers CL:The cancer biomarker problem.Nature 2008,452(7187):548-552.
65.Battling B,Hofmann HS,Weigle B et al:Down-regulation of the receptor for advanced glycation end-products(RAGE) supports non-small cell lung carcinoma.Carcinogenesis 2005,26(2):293-301.
66.Austermann J,Nazmi AR,Muller-Tidow-Cet al:Characterization of the Ca2+ -regulated ezrin-S100P interaction and its role in rumor cell migration,J Biol Chem 2008,283(43):29331-29340.