骨桥蛋白、caspase-3及突变型P53在胶质瘤中的表达研究
|
摘要
目的研究胶质瘤中骨桥蛋白(OPN)、半胱氨酸天冬氨酸蛋白酶-3(caspase-3)和突变型P53(mt-P53)蛋白的表达意义和相关性。方法选取脑胶质瘤(胶质瘤组)患者的标本70例,非脑胶质瘤脑组织10例作为对照组。应用免疫组织化学SP法检测2组OPN、caspase-3及mt-P53蛋白的阳性表达率。蛋白免疫印迹法检测脑胶质瘤中OPN、caspase-3和mt-P53蛋白表达与脑胶质瘤级别的关系。Spearman等级相关分析OPN、caspase-3和mt-P53表达阳性的关系。结果脑胶质瘤组OPN、mt-P53阳性表达率(64.29%和60%)均高于对照组(无阳性表达),caspase-3阳性率低于对照组(47.14%vs.90%),差异有统计学意义(均P<0.05)。OPN、caspase-3和mt-P53在脑胶质瘤不同性别、年龄、肿瘤大小及肿瘤部位组间的阳性表达率差异无统计学意义(P>0.05)。胶质瘤分级越高,OPN和mt-P53的阳性表达率越高,而caspase-3的阳性表达率越低(均P<0.001)。随着脑胶质瘤级别的增加,OPN和mt-P53蛋白表达水平上调,而caspase-3的蛋白表达水平下降。OPN与caspase-3阳性表达呈负相关,与mt-P53表达呈正相关(rs分别为-0.720和0.722,P<0.05),caspase-3和mt-P53表达呈负相关(rs=-0.556,P<0.05)。结论胶质瘤分级越高,OPN和mt-P53的阳性表达率越高,而caspase-3的阳性表达率越低;三者与胶质瘤发生、发展均密切相关,联合检测有助于对胶质瘤生物学行为的判断。
Objective To study the expressions of osteopontin(OPN),caspase-3 and mt-P53 proteins, and their relationshipin gliomas. Methods Seventy gliomas specimens of patients(glioma group) were selected, and 10 samples of non-glioma braintissue were used as control group. The SP method was used to detect the positive rates of protein expressions of OPN, caspase-3 and mt-P53 between two groups. The relationship between protein expressions of OPN, caspase-3 and mt-P53 in gliomas andgrade of gliomas were detected by Western blot assay. Spearman rank correlation was compared between the positive expressionof OPN, caspase-3 and rate mt-P53. Results The positive expression rates of OPN and mt-P53 were significantly higher inglioma group(64.29% and 60%) than those of control group(no positive expression), but the positive expression rate of caspase-3 was significantly lower than that of control group(47.14% vs. 90%, P<0.05). There were no significant differences in OPN,caspase-3 and mt-P53 expressions between different gender, age, tumor size and tumor position(P > 0.05). The higher the WHOclassification, the higher the positive expression rates of OPN and mt-P53(P < 0.001), and the lower the positive expression rateof caspase-3(P < 0.001). With the increased level of glioma grade, OPN and mt-P53 protein levels were increased, but caspase-3 protein expression level was decreased. There was a negatively correlation between OPN and the positive expression of caspase-3, but there was a positive correlation between OPN and the expression of mt-P53(rs=-0.720 and 0.722, P < 0.05). There wasa negative correlation between caspase-3 and mt-P53 expressions(rs=-0.556, P < 0.05). Conclusion The higher the WHOclassification, the higher the positive expression rates of OPN and mt-P53, while the lower the positive expression rate of caspase-3. The study reveals that OPN, caspase-3 and mt-P53 expressions are associated with the occurrence and the progress of gliomas.The combined detection of them can contribute to the judgment of biological behavior of gliomas.
Objective To study the expressions of osteopontin(OPN),caspase-3 and mt-P53 proteins, and their relationshipin gliomas. Methods Seventy gliomas specimens of patients(glioma group) were selected, and 10 samples of non-glioma braintissue were used as control group. The SP method was used to detect the positive rates of protein expressions of OPN, caspase-3 and mt-P53 between two groups. The relationship between protein expressions of OPN, caspase-3 and mt-P53 in gliomas andgrade of gliomas were detected by Western blot assay. Spearman rank correlation was compared between the positive expressionof OPN, caspase-3 and rate mt-P53. Results The positive expression rates of OPN and mt-P53 were significantly higher inglioma group(64.29% and 60%) than those of control group(no positive expression), but the positive expression rate of caspase-3 was significantly lower than that of control group(47.14% vs. 90%, P<0.05). There were no significant differences in OPN,caspase-3 and mt-P53 expressions between different gender, age, tumor size and tumor position(P > 0.05). The higher the WHOclassification, the higher the positive expression rates of OPN and mt-P53(P < 0.001), and the lower the positive expression rateof caspase-3(P < 0.001). With the increased level of glioma grade, OPN and mt-P53 protein levels were increased, but caspase-3 protein expression level was decreased. There was a negatively correlation between OPN and the positive expression of caspase-3, but there was a positive correlation between OPN and the expression of mt-P53(rs=-0.720 and 0.722, P < 0.05). There wasa negative correlation between caspase-3 and mt-P53 expressions(rs=-0.556, P < 0.05). Conclusion The higher the WHOclassification, the higher the positive expression rates of OPN and mt-P53, while the lower the positive expression rate of caspase-3. The study reveals that OPN, caspase-3 and mt-P53 expressions are associated with the occurrence and the progress of gliomas.The combined detection of them can contribute to the judgment of biological behavior of gliomas.
引文
[1]Xu GZ,Du H,Gao BC,et al.Factors related to more malignantglioma prognosis[J].Chinese Journal of Neurosurgery,2011,27(10):1040-1044.[徐国政,杜浩,高宝成,等.恶性脑胶质瘤预后相关多因素分析[J].中华神经外科杂志,2011,27(10):1040-1044].
[2]Yang G,Zhang S,Zhang Y,et al.The inhibitory effects ofextracellular ATP on the growth of nasopharyngeal carcinoma cellsvia P2Y2 receptor and osteopontin[J].J Exp Clin Cancer Res,2014,33(1):53.doi:10.1186/1756-9966-33-53.
[3]Li CL,Chang L,Guo L,et al.β-elemene induces caspase-dependent apoptosis in human glioma cells in vitro through theupregulation of bax and fas/fas L and downregulation of Bcl-2[J].Asian Pac J Cancer Prev,2014,15(23):10407-10412.
[4]Dong P,Karaayvaz M,Jia N,et al.Mutant p53 gain-of-functioninduces epithelial-mesenchymal transition through modulation ofthe mi R-1306-ZEB1 axis[J].Oncogene,2013,32(27):3286-3295.doi:10.1038/onc.2012.334.
[5]Li J,Yang GZ,Zhu ZM,et al.Osteopontin is overexpressed incolorectal carcinoma and is correlated with P53 byimmunohistochemistry[J].Exp Ther Med,2012,3(4):621-624.
[6]Huang H,Zhang XF,Zhou HJ,et al.Expression and prognosticsignificance of osteopontin and caspase-3 in hepatocellularcarcinoma patients after curative resection[J].Cancer Sci,2010,101(5):1314-1319.
[7]Remmele W,Stegner HE.Recommendation for uniform definitionof an immunoreactive score(IRS)for immunohistochemicalestrogen receptor detection(ER-ICA)in breast cancer tissue[J].Pathology,1987,8(3):138-140.
[8]Maeda N,Ohashi T,Chagan-Yasutan H,et al.Osteopontin-integrin interaction as a novel molecular target for antibody-mediated immunotherapy in adult T-cell leukemia[J].Retrovirology,2015,12(1):99-104.
[9]Jan HJ,Lee CC,Shih YL,et al.Osteopontin regulates humanglioma cell invasiveness and tumor growth in mice[J].NeuroOncol,2010,12(1):58-70.doi:10.1093/neuonc/nop013.
[10]Wang XM,Li J,Yan MX,et al.Integrative analyses identifyosteopontin,LAMB3 and ITGB1 as critical pro-metastatic genes forlung cancer[J].PLo S One,2013,8(2):e55714.doi:10.1371/journal.pone.0055714.
[11]Lu DY,Yeh WL,Huang SM,et al.Osteopontin increases heme oxygenase-1 expression and subsequently induces cell migration and invasion in glioma cells[J].Neuro Oncol,2012,14(11):1367-1378.doi:10.1093/neuonc/nos262.
[12]Jin Y,Tong DY,Tang LY,et al.Expressions of osteopontin(OPN),ανβ3 and Pim-1 associated with poor prognosis in nonsmall cell lung cancer(NSCLC)[J].Chin J Cancer Res,2012,24(2):103-108.doi:10.1007/s11670-012-0103-1.
[13]Simpson KL,Cawthorne C,Zhou C,et al.A caspase-3‘deathswitch’in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers[J].Cell Death Dis,2013,4:e613.
[14]Ma ZS,Dai YC,Xie BJ,et al.Expression and significance of HIF-1αand Caspase-3 in breast cancer[J].Modern Oncology,2011,19(11):2216-2219.[马兆生,戴岳楚,谢伯剑,等.HIF-1α与Caspase-3在乳腺癌中的表达及临床病理意义[J].现代肿瘤医学,2011,19(11):2216-2219].doi:10.3969/j.issn.1672-4992.2011.11.25.
[15]Bellini MF,Cury PM,Silva AE.Expression of Ki-67 antigen and caspase-3 protein in benign lesions and esophageal carcinoma[J].Anticancer Res,2010,30(7):2845-2849.
[16]Wang JJ,Sun BC.The expression and significance of caspase-3and caspase-9 in Breast cancer[J].Chinese Journal of Clinical and Experimental Pathology,2012,28(4):378-381.[王进京,孙保存.乳腺癌中caspase-3和caspase-9的表达及其意义[J].临床与实验病理学杂志,2012,28(4):378-381].
[17]Lane DP.The role of mutant P53 in human cancer[J].J Pathol,2011,223(2):116-126.doi:10.1002/path.2784.
[18]Su XL,Li XM,Tian WH,et al.The expression and significance of Aurora-A mt-P53 and c-myc in Colorectal cancer[J].Chinese Journal of Clinical Oncology,2014,41(3):170-174.[苏晓路,李晓鸣,田卫华,等.Aurora-A mt-P53和c-myc在大肠癌中的表达及意义[J].中国肿瘤临床,2014,41(3):170-174].doi:10.3969/j.issn.1000-8179.20131265.
[19]Walerych D,Napoli M,Collavin L,et al.The rebel angel:mutant p53 as the driving oncogene in breast cancer[J].Carcinogenesis,2012,33(11):2007-2017.doi:10.1093/carcin/bgs232.
[20]Vaughan CA,Singh S,Windle B,et al.Gain-of-function activity of mutant p53 in lung cancer through up-regulation of receptor protein tyrosine kinase Axl[J].Genes Cancer,2012,3(7/8):491-502.
[21]Muller PA,Trinidad AG,Timpson P,et al.Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion[J].Oncogene,2013,32(10):1252-1265.doi:10.1038/onc.2012.148.
[2]Yang G,Zhang S,Zhang Y,et al.The inhibitory effects ofextracellular ATP on the growth of nasopharyngeal carcinoma cellsvia P2Y2 receptor and osteopontin[J].J Exp Clin Cancer Res,2014,33(1):53.doi:10.1186/1756-9966-33-53.
[3]Li CL,Chang L,Guo L,et al.β-elemene induces caspase-dependent apoptosis in human glioma cells in vitro through theupregulation of bax and fas/fas L and downregulation of Bcl-2[J].Asian Pac J Cancer Prev,2014,15(23):10407-10412.
[4]Dong P,Karaayvaz M,Jia N,et al.Mutant p53 gain-of-functioninduces epithelial-mesenchymal transition through modulation ofthe mi R-1306-ZEB1 axis[J].Oncogene,2013,32(27):3286-3295.doi:10.1038/onc.2012.334.
[5]Li J,Yang GZ,Zhu ZM,et al.Osteopontin is overexpressed incolorectal carcinoma and is correlated with P53 byimmunohistochemistry[J].Exp Ther Med,2012,3(4):621-624.
[6]Huang H,Zhang XF,Zhou HJ,et al.Expression and prognosticsignificance of osteopontin and caspase-3 in hepatocellularcarcinoma patients after curative resection[J].Cancer Sci,2010,101(5):1314-1319.
[7]Remmele W,Stegner HE.Recommendation for uniform definitionof an immunoreactive score(IRS)for immunohistochemicalestrogen receptor detection(ER-ICA)in breast cancer tissue[J].Pathology,1987,8(3):138-140.
[8]Maeda N,Ohashi T,Chagan-Yasutan H,et al.Osteopontin-integrin interaction as a novel molecular target for antibody-mediated immunotherapy in adult T-cell leukemia[J].Retrovirology,2015,12(1):99-104.
[9]Jan HJ,Lee CC,Shih YL,et al.Osteopontin regulates humanglioma cell invasiveness and tumor growth in mice[J].NeuroOncol,2010,12(1):58-70.doi:10.1093/neuonc/nop013.
[10]Wang XM,Li J,Yan MX,et al.Integrative analyses identifyosteopontin,LAMB3 and ITGB1 as critical pro-metastatic genes forlung cancer[J].PLo S One,2013,8(2):e55714.doi:10.1371/journal.pone.0055714.
[11]Lu DY,Yeh WL,Huang SM,et al.Osteopontin increases heme oxygenase-1 expression and subsequently induces cell migration and invasion in glioma cells[J].Neuro Oncol,2012,14(11):1367-1378.doi:10.1093/neuonc/nos262.
[12]Jin Y,Tong DY,Tang LY,et al.Expressions of osteopontin(OPN),ανβ3 and Pim-1 associated with poor prognosis in nonsmall cell lung cancer(NSCLC)[J].Chin J Cancer Res,2012,24(2):103-108.doi:10.1007/s11670-012-0103-1.
[13]Simpson KL,Cawthorne C,Zhou C,et al.A caspase-3‘deathswitch’in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers[J].Cell Death Dis,2013,4:e613.
[14]Ma ZS,Dai YC,Xie BJ,et al.Expression and significance of HIF-1αand Caspase-3 in breast cancer[J].Modern Oncology,2011,19(11):2216-2219.[马兆生,戴岳楚,谢伯剑,等.HIF-1α与Caspase-3在乳腺癌中的表达及临床病理意义[J].现代肿瘤医学,2011,19(11):2216-2219].doi:10.3969/j.issn.1672-4992.2011.11.25.
[15]Bellini MF,Cury PM,Silva AE.Expression of Ki-67 antigen and caspase-3 protein in benign lesions and esophageal carcinoma[J].Anticancer Res,2010,30(7):2845-2849.
[16]Wang JJ,Sun BC.The expression and significance of caspase-3and caspase-9 in Breast cancer[J].Chinese Journal of Clinical and Experimental Pathology,2012,28(4):378-381.[王进京,孙保存.乳腺癌中caspase-3和caspase-9的表达及其意义[J].临床与实验病理学杂志,2012,28(4):378-381].
[17]Lane DP.The role of mutant P53 in human cancer[J].J Pathol,2011,223(2):116-126.doi:10.1002/path.2784.
[18]Su XL,Li XM,Tian WH,et al.The expression and significance of Aurora-A mt-P53 and c-myc in Colorectal cancer[J].Chinese Journal of Clinical Oncology,2014,41(3):170-174.[苏晓路,李晓鸣,田卫华,等.Aurora-A mt-P53和c-myc在大肠癌中的表达及意义[J].中国肿瘤临床,2014,41(3):170-174].doi:10.3969/j.issn.1000-8179.20131265.
[19]Walerych D,Napoli M,Collavin L,et al.The rebel angel:mutant p53 as the driving oncogene in breast cancer[J].Carcinogenesis,2012,33(11):2007-2017.doi:10.1093/carcin/bgs232.
[20]Vaughan CA,Singh S,Windle B,et al.Gain-of-function activity of mutant p53 in lung cancer through up-regulation of receptor protein tyrosine kinase Axl[J].Genes Cancer,2012,3(7/8):491-502.
[21]Muller PA,Trinidad AG,Timpson P,et al.Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion[J].Oncogene,2013,32(10):1252-1265.doi:10.1038/onc.2012.148.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |