Over-expression of survivin and VEGF in small-cell lung cancer may predict the poorer prognosis

Abstract

The expression of survivin, an inhibitor of apoptosis can be seen in most tumors and is correlated with the angiogenic factor vascular endothelial growth factor (VEGF). But little is known about their contribution in small-cell lung cancer (SCLC). This study was designed to investigate the expression of survivin and VEGF in SCLC, and to explore their correlation with clinical-pathological feature and prognosis. Forty-five patients with pathological histology of SCLC were entered into this study. Forty-five cases of matched adjacent non-tumor samples and 10 samples of operated patients with benign lung tumor were also included as control. The expression of survivin and VEGF was detected by immunohistochemistry (IHC, SP). These two sets of data were processed and tested for correlation with major patients' characteristics, and overall survival. The correlations between survivin and VEGF expressions and the clinical-pathological features were evaluated by chi-square test. The correlation between survivin and VEGF expressions was analyzed by Spearman's rank correlation test; the overall survival was analyzed by the Kaplan-Meier method; and the relationship between clinical and pathological features and overall survival was analyzed by the Cox proportional hazard models. Positive expression rate of survivin and VEGF was significantly higher in SCLC than those of adjacent non-tumor tissues and benign lung tumor tissues (73.3 vs. 15.6 vs. 0 %, P < 0.05) and (75.6 vs. 20 vs. 0 %, P < 0.05), respectively. Survivin and VEGF expressions were significantly associated with lymph node metastasis (P = 0.003, 0.011) and clinical stage (P = 0.006, 0.021). The expression of survivin was significantly coincident with the expression of VEGF (r = 0.644, P = 0.000). The median overall survival in survivin positive group and VEGF positive group was significantly shorter than those in survivin negative and VEGF negative group, respectively (log-rank P = 0.000). Moreover, multivariate analysis showed that survivin expression (HR 0.224; 95 % CI 0.074-0.675; P = 0.008) and VEGF expression (HR 0.172; 95 % CI 0.054-0.559; P = 0.003) were statistically independent predictive factors of poorer prognosis for SCLC patients. Our results indicated that survivin and VEGF were over-expressed in small-cell lung cancer, each of them may be an independent poor prognostic factor.