基于TCGA数据库和免疫组化法对整合素β4与肺腺癌的关系研究
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摘要
目的研究肺腺癌组织中整合素β4 mRNA和蛋白的表达情况,并分析其对肺腺癌患者预后的影响。方法通过TCGA数据库中肺腺癌患者的临床和mRNA数据,分析整合素β4 mRNA在肺腺癌与癌旁正常组织中的表达差异,以及对肺腺癌患者的预后影响。通过免疫组化的方法,对20例肺腺癌患者的肺腺癌组织及相应癌旁正常组织中的整合素β4蛋白进行检测,分析整合素β4蛋白在肺腺癌与癌旁正常组织中的表达差异,以及对肺腺癌患者的预后影响。结果整合素β4 mRNA与蛋白在肺腺癌组织的表达水平均高于在癌旁正常组织的表达水平(均P<0.05)。整合素β4蛋白在T2～3期肺腺癌患者癌组织中的表达水平高于在T1期肺腺癌患者癌组织中的表达水平(P<0.05)。肺腺癌组织整合素β4 mRNA高表达患者5年生存率明显低于低表达患者(22.4%vs44.1%,P<0.05),蛋白高表达患者5年生存率亦明显低于低表达患者(25.0%vs 57.1%,P<0.05)。结论整合素β4在肺腺癌组织中表达上调,且高表达的患者预后较差。整合素β4或可作为治疗肺腺癌患者新的潜在靶点和预后指标。
Objective To investigate the expression of integrin β4 in lung adenocarcinoma and its relation with prognosis of patients. Methods The clinical and mRNA data of lung adenocarcinoma patients in TCGA database were used to analyze the differential expression of integrin β4 mRNA between lung adenocarcinoma and adjacent tissues. The expression of integrin β4 protein in cancer and adjacent tissues of 20 patients with lung adenocarcinoma tissues was detected by immunohistochemical method and its relation with prognosis of patients was analyzed. Results The expression levels of integrin β4 mRNA(P<0.05) and protein( P<0.05) in lung adenocarcinoma tissues were higher than those in adjacent tissues. The expression level of integrin β4 protein in cancer tissues of patients with stage T2-3 was higher than that of patients with stage T1(P<0.05). The 5-year survival rate of patients with high expression of integrin β4 mRNA and protein was significantly lower than that of patients with low expression of integrin β4(22.4% vs 44.1%, P<0.05; and 25.0% vs 57.1%, P<0.05, respectively). Conclusion Integrin β4 expression level is up-regulated in lung adenocarcinoma tissue, and the prognosis of patients with high integrin β4 expression is poor, indicating that integrin β4 may be used as a potential target and prognostic indicator for lung adenocarcinoma patients.
Objective To investigate the expression of integrin β4 in lung adenocarcinoma and its relation with prognosis of patients. Methods The clinical and mRNA data of lung adenocarcinoma patients in TCGA database were used to analyze the differential expression of integrin β4 mRNA between lung adenocarcinoma and adjacent tissues. The expression of integrin β4 protein in cancer and adjacent tissues of 20 patients with lung adenocarcinoma tissues was detected by immunohistochemical method and its relation with prognosis of patients was analyzed. Results The expression levels of integrin β4 mRNA(P<0.05) and protein( P<0.05) in lung adenocarcinoma tissues were higher than those in adjacent tissues. The expression level of integrin β4 protein in cancer tissues of patients with stage T2-3 was higher than that of patients with stage T1(P<0.05). The 5-year survival rate of patients with high expression of integrin β4 mRNA and protein was significantly lower than that of patients with low expression of integrin β4(22.4% vs 44.1%, P<0.05; and 25.0% vs 57.1%, P<0.05, respectively). Conclusion Integrin β4 expression level is up-regulated in lung adenocarcinoma tissue, and the prognosis of patients with high integrin β4 expression is poor, indicating that integrin β4 may be used as a potential target and prognostic indicator for lung adenocarcinoma patients.
引文
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[2]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA:ACancer Journal for Clinicians,2016,66(2):115-132.DOI:10.3322/caac.21338.
[3]Toh CK,Gao F,Lim WT,et al.Never-Smokers With Lung Cancer:Epidemiologic Evidence of a Distinct Disease Entity[J].Journal of Clinical Oncology,2006,24(15):2245-2251.DOI:10.1200/JCO.2005.04.8033.
[4]Shintani T,Matsuo Y,Iizuka Y,et al.Prognostic Significance of Serum CEA for Non-small Cell Lung Cancer Patients Receiving Stereotactic Body Radiotherapy[J].Anticancer research,2017,37(9):5161-5167.DOI:10.21873/anticanres.11937.
[5]Shaw AT,Kim DW,Nakagawa K,et al.Crizotinib versus chemotherapy in advanced ALK-positive lung cancer[J].N Engl J Med,2013,368(25):2385-2394.DOI:10.1056/NEJMoa1214886.
[6]Chou WC,Huang SF,Yeh KY,et al.Different Responses to Gefitinib in Lung Adenocarcinoma Coexpressing Mutant-and Wild-Type Epidermal Growth Factor Receptor Genes[J].Japanese Journal of Clinical Oncology,2006,36(8):523-526.DOI:10.1093/jjco/hyl057.
[7]Bhattacharjee A,Meyerson M.Classification of Human Lung Carcinomas by mRNA Expression Profiling[M].Expression Profiling of Human Tumors.Humana Press,2003.
[8]Beer DG,Kardia SLR,Huang CC,et al.Gene-expression profiles predict survival of patients with lung adenocarcinoma[J].Nature Medicine,2002,8:4.DOI:10.1038/nm733.
[9]Larsen JE,Pavey SJ,Passmore LH,et al.Gene expression signature predicts recurrence in lung adenocarcinoma[J].Clinical Cancer Research,2007,13(10):2946-2954.DOI:10.1158/1078-0432.CCR-06-2525.
[10]Stewart RL,O'Connor KL.Clinical significance of the integrinα6β4in human malignancies[J].Laboratory Investigation,2015,95(9):976-986.DOI:10.1038/labinvest.2015.82.
[11]Wilhelmsen K,Litjens SHM,Sonnenberg A.Multiple Functions of the Integrinalα6β4 in Epidermal Homeostasis and Tumorigenesis[J].Molecular and Cellular Biology,2006,26(8):2877-2886.DOI:10.1128/MCB.26.8.2877-2886.2006.
[12]Guo W,Giancotti FG.Integrin signalling during tumour progression[J].Nature Reviews Molecular Cell Biology,2004,5(10):816-826.DOI:10.1038/nrm1490.
[13]Huttenlocher A,Lakonishok M,Kinder M,et al.Integrin and Cadherin Synergy Regulates Contact Inhibition of Migration and Motile Activity[J].The Journal of Cell Biology,1998,141(2):515-526.DOI:10.1083/jcb.141.2.515.
[14]Lu S,Simin K,Khan A,et al.Analysis of Integrin beta4 Expression in Human Breast Cancer:Association with Basallike Tumors and Prognostic Significance[J].Clinical Cancer Research,2008,14(4):1050-1058.DOI:10.1158/1078-0432.CCR-07-4116.
[15]Grossman HB,Lee C,Bromberg J,et al.Expression of the alpha6beta4integrin provides prognostic information in bladder cancer[J].Oncology Reports,2000,7(1):13-16.DOI:10.3892/or.7.1.13.
[16]Carico E,French D,Bucci B,et al.Integrin beta 4 expression in the neoplastic progression of cervical epithelium[J].Gynecologic Oncology,1993,49(1):61-66.DOI:10.1006/gyno.1993.1087.
[17]Eriksen JG,Steiniche T,Sogaard H,et al.Expression of integrins and E-cadherin in squamous cell carcinomas of the head and neck[J].Apmis,2004,112(9):560-568.DOI:10.1111/j.1600-0463.2004.apm1120902.x.
[18]Mariani Costantini R,Falcioni R,Battista P,et al.Integrin(α6/β4)Expression in Human Lung Cancer as Monitored by Specific Monoclonal Antibodies[J].Cancer Research,1990,50(18):6107.DOI:REVINF-04-2009-58-149-1293-8505-101019-200902133.
[19]Camp RL,Dolled-Filhart M,Rimm DL.X-Tile:A New Bio-Informatics Tool for Biomarker Assessment and Outcome-Based Cut-Point Optimization[J].Clinical Cancer Research,2004,10(21):7252-7259.DOI:10.1158/1078-0432.CCR-04-0713.
[20]Stewart RL,West D,Wang C,et al.Elevated integrinα6β4expression is associated with venous invasion and decreased overall survival in non-small cell lung cancer[J].Human Pathology,2016,54:174-183.DOI:10.1016/j.humpath.2016.04.003.