Reduced XPC messenger RNA level may predict a poor outcome of patients with nonsmall cell lung cancer

Abstract

Homologous deletion of the xeroderma pigmentosum complementary group C (XPC) repair gene frequently causes lung adenocarcinoma in mice, suggesting that an XPC defect may play a critical role in lung tumorigenesis. The current study attempted to determine whether reduced XPC mRNA levels predict the clinical outcome of lung cancer patients. XPC, p27(kip) (cdk inhibitory protein), and S-phase kinase-associated protein (skp2) levels were evaluated by Western blot analysis in a series of lung cancer cell lines with different invasive abilities. Migration and invasive abilities were measured using a modified Boyden chamber without and with Matrigel, respectively. To test whether XPC affects cell invasive ability, XPC gene protein expression was reduced in low invasive cells by RNA interference (RNAi) and assayed with Boyden chamber. XPC mRNA levels in 126 nonsmall cell lung cancers (NSCLCs) were examined by real-time-reverse-transcriptase polymerase chain reaction (RT-PCR). The prognostic value of XPC mRNA expression was statistically analyzed by the Kaplan-Meier method and Cox proportional hazards regression. The expression of XPC was reduced with increasing invasive potential in CL1-series lung cancer cell lines. When the XPC level was reduced by RNAi, cell migration and invasiveness increased markedly; the increased invasiveness may be caused by decreased expression of p27(kip) and increased expression of skp2 and E2F transcription factor 1. To determine whether reduced XPC expression was correlated with tumor aggressiveness and poor patient survival, XPC mRNA levels were evaluated by real-time RT-PCR. Kaplan-Meier analysis demonstrated that the median survival of patients with lower XPC mRNA levels was shorter compared with patients with higher XPC mRNA levels (P = .0440). Cox regression analysis further indicated that XPC mRNA level may act as an independent prognostic factor for NSCLC patients (P = .014). The results of the current study suggest that reduced XPC mRNA level may constitute an independent prognostic factor for NSCLC patients.