卵巢癌中Tiam1蛋白过表达的临床病理学意义
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摘要
目的探讨卵巢癌中Tiam1过表达的临床病理学意义。方法采用免疫组化SP两步法检测Tiam1蛋白在98例浆液性卵巢癌组织、64例黏液性囊腺癌组织以及27例良性病变组织中的表达,并分析其过表达与卵巢癌临床病理特征的关系。应用Kaplan-Meier进行生存分析。结果 Tiam1蛋白主要表达于卵巢癌细胞胞质和胞核中。在浆液性卵巢癌组织中,Tiam1蛋白的阳性率和强阳性率分别为84.7%(83/98)和70.4%(69/98);在黏液性囊腺癌组织中,Tiam1蛋白的阳性率和强阳性率分别为87.5%(56/64)和73.4%(47/64),显著高于良性卵巢肿瘤组织(22.2%和7.4%)(P均<0.01)。Tiam1蛋白表达水平与卵巢癌组织学分级、FIGO分期和转移情况密切相关(P均<0.05);与患者年龄及绝经情况无关(P均>0.05)。Kaplan-Meier生存分析显示,Tiam1蛋白高表达的卵巢癌患者总生存期和无瘤生存期均明显低于Tiam1蛋白低表达患者(P均<0.05),且Tiam1蛋白高表达的转移性卵巢癌患者总生存期也明显低于Tiam1蛋白低表达患者(P<0.05)。结论 Tiam1蛋白在卵巢癌组织中明显高表达,其表达水平与卵巢癌患者的预后密切相关。
Purpose To investigate the clinicopathological significance of Tiam1 overexpression in ovarian carcinoma.Methods Tiam1 protein was detected in 98 serous carcinomas,64 ovarian mucinous cystadenocarcinomas and 27 benign ovarian tumors using immunohistochemical of SP two-step staining. Correlations between Tiam1 overexpression and clinicopathological features of ovarian carcinoma were evaluated. Overall survival and disease-free survival rates of ovarian carcinoma patients were calculated by Kaplan-Meier method. Results Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. The positive rate and strongly positive rate of Tiam1 protein were 84. 7%( 83/98) and 70. 4%( 69/98) in serous carcinoma,the positive rate and strongly positive rate of Tiam1 protein were 87. 5%( 56/64) and 73. 4%( 47/64) in ovarian mucinous cystadenocarcinoma,both of which were significantly higher than those in benign ovarian tumor( both P < 0. 01).High-level expression of Tiam1 was positively correlated with the histological grade,FIGO stage,and metastasis in ovarian carcinoma( both P < 0. 05),while independent of age and menopausal status( both P > 0. 05). Kaplan-Meier survival analysis showed that overall survival and disease-free survival of ovarian cancer patients with high expression of Tiam1 protein were significantly lower than those of patients with lower expression of Tiam1 protein( P < 0. 05),overall survival in metastatic ovarian cancer patients with high expression of Tiam1 protein was significantly lower than those in patients with low Tiam1 protein expression( P < 0. 05). Conclusion Tiam1 expression is significantly high in ovarian carcinoma. Tiam1 protein is closely associated with ovarian carcinoma progression,which may be a new potential prognostic biomarker and a therapeutic target for ovarian carcinoma.
Purpose To investigate the clinicopathological significance of Tiam1 overexpression in ovarian carcinoma.Methods Tiam1 protein was detected in 98 serous carcinomas,64 ovarian mucinous cystadenocarcinomas and 27 benign ovarian tumors using immunohistochemical of SP two-step staining. Correlations between Tiam1 overexpression and clinicopathological features of ovarian carcinoma were evaluated. Overall survival and disease-free survival rates of ovarian carcinoma patients were calculated by Kaplan-Meier method. Results Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. The positive rate and strongly positive rate of Tiam1 protein were 84. 7%( 83/98) and 70. 4%( 69/98) in serous carcinoma,the positive rate and strongly positive rate of Tiam1 protein were 87. 5%( 56/64) and 73. 4%( 47/64) in ovarian mucinous cystadenocarcinoma,both of which were significantly higher than those in benign ovarian tumor( both P < 0. 01).High-level expression of Tiam1 was positively correlated with the histological grade,FIGO stage,and metastasis in ovarian carcinoma( both P < 0. 05),while independent of age and menopausal status( both P > 0. 05). Kaplan-Meier survival analysis showed that overall survival and disease-free survival of ovarian cancer patients with high expression of Tiam1 protein were significantly lower than those of patients with lower expression of Tiam1 protein( P < 0. 05),overall survival in metastatic ovarian cancer patients with high expression of Tiam1 protein was significantly lower than those in patients with low Tiam1 protein expression( P < 0. 05). Conclusion Tiam1 expression is significantly high in ovarian carcinoma. Tiam1 protein is closely associated with ovarian carcinoma progression,which may be a new potential prognostic biomarker and a therapeutic target for ovarian carcinoma.
引文
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[8]Bourguignon L Y,Zhu H,Shao L,et al.Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration[J].J Cell Biol,2000,150(1):177-191.
[9]Li Z,Liu Q,Piao J,et al.Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast[J].BMC Cancer,2016,16(1):681.
[10]Li H,Cui X,Chen D,et al.Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma[J].Oncol Lett,2016,12(5):3492-3498.
[11]Mertens A E,Roovers R C,Coilard J G.Regulation of Tiaml-Rac signalling[J].FEBS Lett,2003,546(1):11-16.
[12]Bourguignon L Y,Zhu H,Shao L,et al.Ankyrin-Tiaml interaetion promotes Racl signaling and metastaticbreast tumor cell invasion and migration[J].J Cell Biol,2000,150(1):177-191.
[13]Yu L N,Zhang Q L,Li X,et al.Tiaml transgenic mice display increased tumor invasive and metastatic potential of colorectal cancer after 1,2-dimethylhydrazine treatment[J].PLo S One,2013,8(9):e73077.
[14]Michiels F,Habets G G,Stam J C,et al.A role for Rac in Tiam1-induced membrane ruffling and invasion[J].Nature,1995,375(6529):338-340.
[15]Liu S,Li Y,Qi W,et al.Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients[J].Diagn Pathol,2014,9:69.
[16]Minard M E,Kim L S,Price J E,et al.The role of the guanine nucleotide exchange factor Tiam1 in cellular migration,invasion,adhesion and tumor progression[J].Breast Cancer Res Treat,2004,84(1):21-32.
[17]Li J,Liang S,Jin H,et al.Tiam1,negatively regulated by miR-22,miR-183 and miR-31,is involved in migration,invasion and viability of ovarian cancer cells[J].Oncol Rep,2012,27(6):1835-1842.
[18]张源,杨洋,车拴龙,等.胃腺癌预后评估中Tiaml蛋白过表达的意义[J].临床与实验病理学杂志,2016,32(2):128-130,135.
[19]Wu Q Y,Wang Y,Tong J C,et al.Expression and clinical significance of Tiam1 gene in esophageal carcinoma[J].Int J Clin Exp Med,2015,8(11):21229-21234.
[20]Ding Y,Chen B,Wang S,et al.Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patients[J].Int J Cancer,2009,124(3):653-658.
[2]徐明,杨洋,车拴龙,等.NQO1过表达在卵巢黏液性囊腺癌预后评估中的意义[J].中国病理生理杂志,2016,32(8):1461-1465.
[3]Habets G G,Scholtes E H,Zuydgeest D,et al.Identification of an invasion-inducing gene,Tiam-1,that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins[J].Cell,1994,77(4):537-549.
[4]Cvitkovic E,Bachouchi M,Boussen H,et al.Leukemoid reaction,bone marrow invasion,fever of unknown origin,and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type:a review of 255 consecutive cases[J].J Clin Oncol,1993,11(12):2434-2442.
[5]Engers R,Mueller M,Walter A,et al.Prognostic relevance of Tiam1 protein expression in prostate carcinomas[J].Br J Cancer,2006,95(8):1081-1086.
[6]Qi Y,Huang B,Yu L,et al.Prognostic value of Tiam1 and Rac1overexpression in nasopharyngeal carcinoma[J].ORLJ Otorhinolaryngol Relat Spec,2009,71(3):163-171.
[7]Otsuki Y,Tanaka M,Kamo T,et al.Guanine nucleotide exchange factor,Tiam1,directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 fibroblasts[J].J Biol Chem,2003,278(7):5132-5140.
[8]Bourguignon L Y,Zhu H,Shao L,et al.Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration[J].J Cell Biol,2000,150(1):177-191.
[9]Li Z,Liu Q,Piao J,et al.Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast[J].BMC Cancer,2016,16(1):681.
[10]Li H,Cui X,Chen D,et al.Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma[J].Oncol Lett,2016,12(5):3492-3498.
[11]Mertens A E,Roovers R C,Coilard J G.Regulation of Tiaml-Rac signalling[J].FEBS Lett,2003,546(1):11-16.
[12]Bourguignon L Y,Zhu H,Shao L,et al.Ankyrin-Tiaml interaetion promotes Racl signaling and metastaticbreast tumor cell invasion and migration[J].J Cell Biol,2000,150(1):177-191.
[13]Yu L N,Zhang Q L,Li X,et al.Tiaml transgenic mice display increased tumor invasive and metastatic potential of colorectal cancer after 1,2-dimethylhydrazine treatment[J].PLo S One,2013,8(9):e73077.
[14]Michiels F,Habets G G,Stam J C,et al.A role for Rac in Tiam1-induced membrane ruffling and invasion[J].Nature,1995,375(6529):338-340.
[15]Liu S,Li Y,Qi W,et al.Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients[J].Diagn Pathol,2014,9:69.
[16]Minard M E,Kim L S,Price J E,et al.The role of the guanine nucleotide exchange factor Tiam1 in cellular migration,invasion,adhesion and tumor progression[J].Breast Cancer Res Treat,2004,84(1):21-32.
[17]Li J,Liang S,Jin H,et al.Tiam1,negatively regulated by miR-22,miR-183 and miR-31,is involved in migration,invasion and viability of ovarian cancer cells[J].Oncol Rep,2012,27(6):1835-1842.
[18]张源,杨洋,车拴龙,等.胃腺癌预后评估中Tiaml蛋白过表达的意义[J].临床与实验病理学杂志,2016,32(2):128-130,135.
[19]Wu Q Y,Wang Y,Tong J C,et al.Expression and clinical significance of Tiam1 gene in esophageal carcinoma[J].Int J Clin Exp Med,2015,8(11):21229-21234.
[20]Ding Y,Chen B,Wang S,et al.Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patients[J].Int J Cancer,2009,124(3):653-658.