CREB在乳腺癌病灶组织与血清中的表达与临床意义
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摘要
目的探讨环磷腺苷效应元件结合蛋白(简称CREB)在乳腺癌和乳腺纤维腺瘤患者的病灶组织和血清中的表达情况,并分析其与乳腺癌的各临床因素之间的关系和临床意义。方法 (1)随机选取2017年5月至11月行手术的乳腺癌和乳腺纤维腺瘤的患者各30例,收集两组患者的新鲜病灶组织标本后采用Western Blotting检测其中CREB的含量,利用SPSS 21.0软件对两组数据进行方差分析,比较CREB在乳腺良、恶性病灶组织中的表达情况,并分析其临床意义。(2)同时分别收集上述病例的血清,采用ELISA法检测其CREB的含量,再次对两组数据进行方差分析,比较和分析乳腺癌和乳腺纤维腺瘤患者的血清中CREB的表达情况,并分析其临床意义。(3)在乳腺癌的癌组织及血清组中,均按年龄、肿块大小、淋巴结转移、组织学分级、分期、ER、PR、HER-2、Ki-67进行分组,分别比较血清中、癌组织中CREB的表达与各临床因素之间的关系,均采用独立样本的t检验进行统计学比较。本实验中统计分析均认为P<0.05,差异具有统计学意义。结果 (1)在乳腺癌患者的病灶组织和血清中CREB的表达均高于乳腺纤维腺瘤患者的,上述两组差异均具有统计学意义(P<0.05);(2)在乳腺癌患者的癌组织及血清组中,分别比较其CREB的表达与各临床因素的关系显示:各两组之间的差异均无统计学意义(P值均大于0.05)。结论 CREB在乳腺良、恶性疾病的病灶组织和血清中均表达,但其在乳腺癌的癌灶组织及血清中的表达明显高于乳腺纤维腺瘤的病灶组织及血清中的,这可能对不同的乳腺疾病有一定的诊断意义。另外,在乳腺癌患者中,其癌灶组织和血清中CREB的表达与年龄、肿块大小、淋巴结转移与否、组织学分级高低、ER、PR及HER-2的表达与否、Ki-67高低均无明显的相关性。
Objective To investigate the expression of c AMP response element binding protein(CREB) with the cancerous tissue and serum in breast cancer and fibroadenoma, and analyze it's relationship with clinical factors, and then further explore its clinical significance. Methods(1) There were 30 patients respectively in the two group, each of which was the breast cancer patients and the patients who suffer from breast fibroadenoma, and was randomly selected from May to November 2017. The next steep was collecting these lesion tissue samples in different groups, and then detecting the content of CREB by using Western blotting technique. Finally we used the SPSS 21.0 software to analyze the two groups' data by variance analysis and compare the expression of CREB in breast malignant lesion tissues with the one of benign lesion, and meanwhile we should analyze the clinical significance of the expression of CREB in breast cancer.(2) At the same time, we needed collect the serum samples with patients mentioned above and used the enzyme linked immunosorbent assay to detect the content of CREB about the two groups of data. We needed compare and analyze the expression of serum's CREB in benign and malignant breast diseases by using analysis of variance once more, and further analyzed the clinical significance of the expression of CREB in serum of breast cancer cases.(3)According to the age of patient, tumor size, lymph node metastasis, phase, histological grade, and the experession of the other objects of observation,including ER、PR, HER-2, Ki-67,We respectively divided the breast malignant lesion tissues into two groups,then compared the expression of CREB with all factors and analyzed their clinical significance by using the t test of independent samples. The same methods and principles were applied to the serum of the breast cancer's patients. If the statistical analysis showed that P was less than 0.05, we can think that the difference is statistical significant. Results(1)We found that it has difference about the expression of CREB in both tissues and serum between breast cancer and the breast fibroadenoma, and the difference has a notable statistical significant(P<0.000). So we think the result may have a certain diagnostic significance for different breast diseases.(2)According to these objects of clinical observation in the breast cancer tissue and serum, the result showed that there was no statistical difference when compared the expression of CREB between with the each two groups(all of these P-values were greater than 0.05). Conclusion So we think the expression of CREB in cancerous tissue and serum may be not related to the age、tumor size、lymph node metastasis、histological grade、ER、PR、HER-2, or Ki-67 level.
Objective To investigate the expression of c AMP response element binding protein(CREB) with the cancerous tissue and serum in breast cancer and fibroadenoma, and analyze it's relationship with clinical factors, and then further explore its clinical significance. Methods(1) There were 30 patients respectively in the two group, each of which was the breast cancer patients and the patients who suffer from breast fibroadenoma, and was randomly selected from May to November 2017. The next steep was collecting these lesion tissue samples in different groups, and then detecting the content of CREB by using Western blotting technique. Finally we used the SPSS 21.0 software to analyze the two groups' data by variance analysis and compare the expression of CREB in breast malignant lesion tissues with the one of benign lesion, and meanwhile we should analyze the clinical significance of the expression of CREB in breast cancer.(2) At the same time, we needed collect the serum samples with patients mentioned above and used the enzyme linked immunosorbent assay to detect the content of CREB about the two groups of data. We needed compare and analyze the expression of serum's CREB in benign and malignant breast diseases by using analysis of variance once more, and further analyzed the clinical significance of the expression of CREB in serum of breast cancer cases.(3)According to the age of patient, tumor size, lymph node metastasis, phase, histological grade, and the experession of the other objects of observation,including ER、PR, HER-2, Ki-67,We respectively divided the breast malignant lesion tissues into two groups,then compared the expression of CREB with all factors and analyzed their clinical significance by using the t test of independent samples. The same methods and principles were applied to the serum of the breast cancer's patients. If the statistical analysis showed that P was less than 0.05, we can think that the difference is statistical significant. Results(1)We found that it has difference about the expression of CREB in both tissues and serum between breast cancer and the breast fibroadenoma, and the difference has a notable statistical significant(P<0.000). So we think the result may have a certain diagnostic significance for different breast diseases.(2)According to these objects of clinical observation in the breast cancer tissue and serum, the result showed that there was no statistical difference when compared the expression of CREB between with the each two groups(all of these P-values were greater than 0.05). Conclusion So we think the expression of CREB in cancerous tissue and serum may be not related to the age、tumor size、lymph node metastasis、histological grade、ER、PR、HER-2, or Ki-67 level.
引文
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[2]Wanqing Chen,Ph D,MD1,Rongshou Zheng,MPH2,et al.Cancer Statistics in China,2015[J].CA Cancer J.Clin,2016,66:115-132.
[3]马素珍,石宁,刘丹丹,等.人CREB1基因及蛋白的生物信息学分析[J].生物技术,2016(6):557-565.
[4]Michel M,Kemenes I,Müller U,et al.Different phases of long-term memory require distincnct temporal patterns of PKA activity after single-trial classical conditioning[J].Learn Mem,2008,15(9):694-702.
[5]Caravatta L,Sancilio S,di Giacomo V,et al.PI3K/Akt-dependent activation of c AMP-response element-binding(CREB)protein in Jurkat T leukemia cells treated with TRAIL[J].J Cell Physiol,2008,214(1):192-200.
[6]Flammer JR,Popova KN,Pflum MK.Cyclic AMP responseelement-binding protein(CREB)and CAAT/enhancer-binding protein beta(C/EBPbeta)bind chimeric DNA sites with high affinity[J].Biochemistry,2006,45(31):9615-9623.
[7]Boer U,Eglins J,Krause D,et al.Enhancement by lithium of c AMP-induced CRE/CREB-directed gene transcription conferred by TORC on the CREB basic leucine zipper domain[J].Biochem J,2007,408(1):69-77.
[8]李垒,王萍.转录因子环腺苷酸反应元件结合蛋白介导的细胞凋亡及其调控机制[J].解剖学报,2012,43(01):139-144.
[9]张澄,王萍.转录因子CREB对细胞周期调控机制的研究进展[J].中国细胞生物学学报,2011,33(05):577-583.
[10]Yin J C P,Vecchio M D,Zhou H,et al.CREB as a Memory Modulator:induced expression of a d CREB2 activator isoform enhances long-term memory in drosophila[J].Cell,1995,81(1):107.
[11]Mohamed H A,Yao W,Fioravante D,et al.c AMP-response elements in Aplysia creb1,creb2,and Ap-uch promoters:implications for feedback loops modulating long term memory[J].Journal of Biological Chemistry,2005,280(29):27035-43.
[12]Hao L,Yang Z,Bi Y.Stochasticity and bifurcations in a reduced model with interlinked positive and negative feedback loops of CREB1 and CREB2stimulated by 5-HT[J].Mathematical Biosciences,2016,274:73-82.
[13]Lueptow L M,Zhan C G,O’Donnell J M.Cyclic GMP–mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice[J].Psychopharmacology,2016,233(3):447-456.
[14]Antony N,Mcdougall A R,Mantamadiotis T,et al.Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymalindependent mechanisms[J].Scientific Reports,2016,6:25569.
[15]庄海慧,王雪,王萍.转录因子环腺苷酸反应元件结合蛋白在肿瘤转移中的作用及其分子机制[J].解剖学报,2015,46(01):138-143.
[16]肖佩芳,柴忆欢,何军,等.环磷酸腺苷反应元件结合蛋白在儿童急性淋巴细胞白血病中表达的意义[J].实用儿科临床杂志,2008,(03):200-202.
[17]Mitton B,Chae H-D,Hsu K,et al.Small Molecule Inhibition of c AMP Response Element Binding Protein in Human Acute Myeloid Leukemia Cells[J].Leukemia,2016,30(12):2302-2311.
[18]戎荣,吴妍,宋国新,等.磷酸化CREB蛋白在肝内胆管癌组织中的表达及临床意义[J].江苏医药,2014,40(19):2293-2295+2381.
[19]唐海斌,马越云,苏明权,等.CREB及p-CREB在前列腺癌细胞增殖中的作用[J].中国肿瘤生物治疗杂志,2016,23(02):223-229.
[20]Hye-Sook Seo,Diane D Liu,Ja Seok Koo,et al.Cyclic AMP response element binding protein over expression:A Feature associated with negative prognosis in never smokers with non small cell lung cancer[J].Cancer Res,2008,68(15):6065-6073.
[21]Chhabra,et al.CREB of transcription factor CREB1 in human breast cancer and its correlation Expression with prognosis[J].Oncol Rep,2007,18(4):953-985.
[2]Wanqing Chen,Ph D,MD1,Rongshou Zheng,MPH2,et al.Cancer Statistics in China,2015[J].CA Cancer J.Clin,2016,66:115-132.
[3]马素珍,石宁,刘丹丹,等.人CREB1基因及蛋白的生物信息学分析[J].生物技术,2016(6):557-565.
[4]Michel M,Kemenes I,Müller U,et al.Different phases of long-term memory require distincnct temporal patterns of PKA activity after single-trial classical conditioning[J].Learn Mem,2008,15(9):694-702.
[5]Caravatta L,Sancilio S,di Giacomo V,et al.PI3K/Akt-dependent activation of c AMP-response element-binding(CREB)protein in Jurkat T leukemia cells treated with TRAIL[J].J Cell Physiol,2008,214(1):192-200.
[6]Flammer JR,Popova KN,Pflum MK.Cyclic AMP responseelement-binding protein(CREB)and CAAT/enhancer-binding protein beta(C/EBPbeta)bind chimeric DNA sites with high affinity[J].Biochemistry,2006,45(31):9615-9623.
[7]Boer U,Eglins J,Krause D,et al.Enhancement by lithium of c AMP-induced CRE/CREB-directed gene transcription conferred by TORC on the CREB basic leucine zipper domain[J].Biochem J,2007,408(1):69-77.
[8]李垒,王萍.转录因子环腺苷酸反应元件结合蛋白介导的细胞凋亡及其调控机制[J].解剖学报,2012,43(01):139-144.
[9]张澄,王萍.转录因子CREB对细胞周期调控机制的研究进展[J].中国细胞生物学学报,2011,33(05):577-583.
[10]Yin J C P,Vecchio M D,Zhou H,et al.CREB as a Memory Modulator:induced expression of a d CREB2 activator isoform enhances long-term memory in drosophila[J].Cell,1995,81(1):107.
[11]Mohamed H A,Yao W,Fioravante D,et al.c AMP-response elements in Aplysia creb1,creb2,and Ap-uch promoters:implications for feedback loops modulating long term memory[J].Journal of Biological Chemistry,2005,280(29):27035-43.
[12]Hao L,Yang Z,Bi Y.Stochasticity and bifurcations in a reduced model with interlinked positive and negative feedback loops of CREB1 and CREB2stimulated by 5-HT[J].Mathematical Biosciences,2016,274:73-82.
[13]Lueptow L M,Zhan C G,O’Donnell J M.Cyclic GMP–mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice[J].Psychopharmacology,2016,233(3):447-456.
[14]Antony N,Mcdougall A R,Mantamadiotis T,et al.Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymalindependent mechanisms[J].Scientific Reports,2016,6:25569.
[15]庄海慧,王雪,王萍.转录因子环腺苷酸反应元件结合蛋白在肿瘤转移中的作用及其分子机制[J].解剖学报,2015,46(01):138-143.
[16]肖佩芳,柴忆欢,何军,等.环磷酸腺苷反应元件结合蛋白在儿童急性淋巴细胞白血病中表达的意义[J].实用儿科临床杂志,2008,(03):200-202.
[17]Mitton B,Chae H-D,Hsu K,et al.Small Molecule Inhibition of c AMP Response Element Binding Protein in Human Acute Myeloid Leukemia Cells[J].Leukemia,2016,30(12):2302-2311.
[18]戎荣,吴妍,宋国新,等.磷酸化CREB蛋白在肝内胆管癌组织中的表达及临床意义[J].江苏医药,2014,40(19):2293-2295+2381.
[19]唐海斌,马越云,苏明权,等.CREB及p-CREB在前列腺癌细胞增殖中的作用[J].中国肿瘤生物治疗杂志,2016,23(02):223-229.
[20]Hye-Sook Seo,Diane D Liu,Ja Seok Koo,et al.Cyclic AMP response element binding protein over expression:A Feature associated with negative prognosis in never smokers with non small cell lung cancer[J].Cancer Res,2008,68(15):6065-6073.
[21]Chhabra,et al.CREB of transcription factor CREB1 in human breast cancer and its correlation Expression with prognosis[J].Oncol Rep,2007,18(4):953-985.
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