Prognostic value of survivin, X-linked inhibitor of apoptosis protein and second mitochondria-derived activator of caspases expression in advanced non-small-cell lung cancer patients

Abstract

Background and objective: Survivin and X-linked inhibitor of apoptosis protein (XIAP) in vitro mediate cancer cell survival and chemoresistance. Second mitochondria-derived activator of caspases (Smac), an antagonist of XIAP, has been shown in vitro to increase chemosensitivity. This study examined the prognostic value of survivin, XIAP and Smac in advanced non-small-cell lung cancer (NSCLC) patients treated with cisplatin-containing chemotherapy.

Methods: Semi-quantitative RT-PCR was used to measure survivin, XIAP and Smac mRNA expression in transbronchial biopsy tumour specimens from 72 patients with advanced NSCLC before commencing chemotherapy. Outcome measures were response to chemotherapy, progression-free survival (PFS) and overall survival (OS).

Results: Low expression of survivin was associated with good response to chemotherapy (P = 0.028). No association was found between XIAP and Smac expression levels and response to chemotherapy (P = 0.224 and P = 0.088, respectively). Patients with low survivin expression or high Smac expression had significantly longer PFS (P = 0.012 and P = 0.029, respectively) and OS (P = 0.007 and P = 0.031, respectively) compared with patients with high expression of survivin or low expression of Smac. XIAP expression was not correlated with PFS or OS. Additionally, PFS and OS in patients with performance status of 0 or 1 and stage IIIB were significantly longer than PFS and OS in patients with performance status (PS) of 2 and stage IV disease. Multivariate Cox regression analyses demonstrated that survivin and clinical stage were independent predictors for PFS and OS. Smac was an independent prognostic factor for OS, but not for PFS.

Conclusions: Our findings suggest that the expression levels of survivin and Smac, but not XIAP, predict the survival of patients with advanced NSCLC treated with chemotherapy.