Lymphocytes Infiltrating And The Expression Of CTGF And Their Relationship With Prognosis Of Non-small-cell Lung Cancer

Background and objectiveLung cancer is the most common cause of cancer death in the world. The majority of lung cancers are non-small-cell lung carcinoma (NSCLC), which is subdivided into squamous-cell carcinoma (SC),adenocarcinoma(AC), and large-cell carcinoma, followed by small cell lung cancer.In spite of the combined treatment of surgery,radiotherapy and chemotherapy,the 5-year survival rate remains about 10%,so NSCLC terribly endengers the human life.Tumor microenvironment is composed of tumor cells, extracellular matrix, cytokines, chemokines. Microenvironment of the tumor stroma in tumor progression changes play an important role. The double-edged-sword nature of many tumor-associated immune cells such as macrophages, dendritic cells, and cytotoxic T cells has been recognized.On the one hand, these immune cells may recognize tumor-associated antigen and activate cytotoxic T cells, in order to initiate anti-tumor immune responses. On the other hand, the same immune cells may establish immune tolerance and even promote tumor growth and metastasis through enhancing angiogenesis and invasion of extracellular matrix.Connective tissue growth factor (CTGF) is a secreted protein that belongs to CCN(Cyr61, CTGF, Nov) family. The proteins in this family are implicated in various biological processes,such as angiogenesis,adhesion,migration,and apoptosis.In this study, we explored the roles of t Lymphocytes infiltrating and the expression of CTGF and their relationship with prognosis of non-small-cell lung cancer.Materials and methodPatients and clinical dataThis study 131 cases of non-small cell lung cancer tissue specimen were collected from of Thoracic Surgery in The First Affiliated Hospital of Zhengzhou University form 2004 to 2007 by surgical resection.All of the specimens were pathologically indentified.All patients were not received preoperative chemotherapy and radiotherapy treatment, and no significant heart, kidney, liver and nervous system disorders affect the life.All the patients were followed up by telephone postoperative.The cut off dete is August 31,2010.Calculate the survival time,the day form surgery to death or last follow-up time,based on unit to months.And record the patient's smoking history and family history information.Experimental MethodsAll resected specimens were fixed in 10% formaldehyde, paraffin embedded, 4μm serial sections for SP immunohistochemistry. SP kit, DAB color kit, mouse anti-human CD3 monoclonal antibody, mouse anti-human CTGF monoclonal antibody were Beijing Zhongshan Golden Bridge Biotechnology Company. Steps refer to kit instructions. Antibody was replaced by PBS as a negative control.Statistical analysisAll statistical analyses were performed using the statistical package SPSS, version 17.0. The chi-square test, Kaplan-Merrier survival analysis and Cox multivariate survival analysis. The significance level was set at P< 0.05.Results1.In the follow-up patients for more than three years, the overall survival rate was 50.4%(58/115).2. Expression of CD3 and CTGF and its relationship with clinicopathological features CD3 was widely expressed in NSCLC tissue.The positive prote of CD3 in NSCLC tissue was located in the membrane,tan or brown grain. The positive prote of CTGF in NSCLC tissue was located in the cytoplasm or membrane,tan or brown grain,which could also be seen in interstitial connective tissue and smooth muscle around the cancerous tissue.The expression of CD3 and CTGF in NSCLC were no significant relation with age, gender, histological types and disease stage(P>0.05).3.The expression of CD3 and CTGF were classfied to low expression and high expression two groups. Univariate survival analysis, survival analysis curves showed that,the patients in high ecpression CD3 group was significantly positive correlated with the prognosis of patients.The accumulative total survival rate of patients in high expression group was significantly higher than the low expression group(P=0.004). Survival analysis curve shows, the patients in high ecpression CTGF group was significantly positive correlated with the prognosis of patients.The accumulative total survival rate of patients in high expression group was significantly higher than the low expression group(P=0.033).4.Cox regression model for multivariate survival analysis in NSCLCAll the patients age,gender,histological types, disease stage, CD3 lymphocytes infiltrating and the expression of CTGF in NSCLC tissues for variable factors,the results of Cox regression analysis showed that independent prognostic factors of NSCLC were resection margin(P=0.026),disease stage(P=0.000) and CD3 lymphocytes infiltrating (P=0.011).ConclusionT lymphocytes in tumor tissue density and the expression levels of CTGF and long term survival of patients with a positive correlation can be used as prognostic indicators.