Prognostic significance of STAT3 expression and its correlation with chemoresistance of non-small cell lung cancer cells

Abstract

Activation of signal transducer and activator of transcription 3 (STAT3) plays important roles in tumorigenesis and tumor development. Previously, we have reported that overexpression of STAT3 potentiates growth, survival and radioresistance of non-small cell lung cancer (NSCLC) cells. The aim of this study was to investigate the prognostic significance of STAT3 expression and its correlation with chemoresistance of NSCLC cells. Semi-quantitative RT-PCR was performed to detect the expression of STAT3 mRNA in 12 NSCLC and corresponding adjacent lung tissues. Immunohistochemistry was performed to detect the expression of STAT3 protein in 76 NSCLC tissue samples. Additionally, the correlation between STAT3 expression and prognosis of NSCLC patients was statistically analyzed. The role of STAT3 in chemoresistance of NSCLC cells was also assessed by the vector-based small interfering RNA. The expression level of STAT3 mRNA in NSCLC tissues was significantly higher than that in corresponding adjacent lung tissues (P<0.05). Positive immunostaining of STAT3 protein was mainly located in the cytoplasm of tumor cells. The expression of STAT3 protein was significantly correlated with tumor differentiation, clinical stage and lymph node metastasis of NSCLC patients. Moreover, the 5-year overall survival rate of patients with high STAT3 expression (42.3%) was significantly lower than that of patients with low STAT3 expression (58.8%; P<0.001). Multivariate analysis using the Cox proportional hazard model showed that high STAT3 protein expression was an independent prognostic factor for NSCLC patients (P=0.021). Furthermore, two stably transfected cell lines (A549/shSTAT3 and SPC-A1/shSTAT3) were successfully established, and RNAi-mediated STAT3 inhibition could significantly increase the sensitivity of NSCLC cells to cisplatin by enhancing caspase-3-dependent apoptosis. Together, the expression of STAT3 might be an independent prognostic marker for NSCLC patients and RNAi-mediated STAT3 inhibition would be a potential strategy for chemosensitization of NSCLC cells.