A Study On The Relationship Between The Expression Of Apoptosis-related Oncogenes In NSCLC With Their Clinical And Prognostic Significance

Objective: The prognosis of non-small cell lung cancer (NSCLC) is related to many factors. Apoptosis-related oncogenes play an important role in occurrence and development of tumors. The significance of apoptosis as a biological and prognostic factor has not been clearly established in NSCLC. To the best of our knowledge, no joint analysis of apoptosis in correlation to caspase-3,survivin,k-ras protein status in NSCLC was performed. Therefore, the aim of this study was to assess the relationship between the expression of above proteins in NSCLC with theirs clinicopathological characteristics and prognostic significance and their potential relevance existing in NSCLC.Methods: Archival formalin fixed, paraffin embedded specimens from 91 patients who had undergone radical surgery for NSCLC between July 1999 and July 2005 in Anhui provincial hospital were investigated in this study. Cancer tissue was excised from each surgical specimen and adjacent normal tissue (at least 5 cm from the tumor) was Compared. There were 77 male and 14 female with a median age of 62 years (range 39~78). Caspase-3,survivin,k-ras protein expression were detected in NSCLC tissues and normal lung tissues adjacent to carcinomas by streptavidin-peroxidase immunohistochemistry. Statistical anaysis was performed using SPSS statistical software package(11.0). Survival curves were calculated according to Kaplan–Meier method and compared with the use of log-rank test. Multivariate analysis was based on backward Cox regression model with P values lower than 0.05 considered as statistically significant.Results: The positive rate of caspase-3 was significantly lower in NSCLC than in normal lung tissues adjacent to carcinomas; The positive rate of survivin,k-ras was significantly higher in NSCLC than in normal lung tissues adjacent to carcinomas(P﹤0.001). The positive rate of caspase-3 was related to the age,histologic tye,TNM stage,lymph node metastasia and differentiation (P﹤0.05), but not related to the sex,tumor size,smoke(P﹥0.05); the positive rate of survivin was related to the age,TNM stage,lymph node metastasia and differentiation (P﹤0.05), but not related to sex,histologic tye,tumor size,smoke(P﹥0.05); the positive rate of k-ras was related to the histologic type and smoke(P﹤0.05), but not related the age,TNM stage,lymph node metastasia,differentiation,sex,tumor size(P﹥0.05). Expression of caspase-3 was negatively correlated with survivin(P﹤0.05). The factors with inclusion of survivin,caspase-3,histologic tye,differentiation,TNM stage,lymph node metastasia and smoke were confirmed to be significantly associated with the median survival time of paitents in univariate analysis with Kaplan-Meier mothod (P﹤0.05). The multivariate analysis with Cox hazard model, survivin,caspase-3,histologic tye,differentiation,TNM stage could be independent indicators for the prognosis of patients with NSCLC(P﹤0.05).Conclusions:1.There are over-expressions of survivin,k-ras protein in NSCLC and both are significantly higher than those in the normal tissue. However, caspase-3 presents the reverse result;2. Higher expression of survivin,lower expression of caspase-3,adenocarcinoma type,poorer differentiation,higher TNM stage might be the adverse prognostic index for survival in resected NSCLC patients;3. the relationship between the expression of k-ras and the prognosis of NSCLC is still not clear.