Clinicopathologic features and prognostic implications of Gankyrin protein expression in non-small cell lung cancer

Abstract

PurposeThe expression of Gankyrin, a liver cancer-related oncoprotein, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of Gankyrin expression in NSCLC remains unclear. MethodsGankyrin expression was assessed using immunohistochemical (IHC) methods in 166 paired paraffin-embedded NSCLC specimens and adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were employed to measure the expression of Gankyrin in 24 paired fresh NSCLC specimens and the corresponding normal tissues. The association of Gankyrin expression with clinicopathological parameters was also evaluated. Kaplan–Meier survival analysis and Cox proportional hazards models were used to estimate the effect of Gankyrin expression on survival. ResultsData showed that Gankyrin was expressed in 78.3% (130/166) and 28.9% (48/166) of cancer lesions and corresponding adjacent normal tissue, respectively. And the Gankyrin overexpression in tumor tissue occurred in 53.6% (89/166) of patients, while overexpression of Gankyrin in normal tissue occurred only in 4.8% (8/166) of patients (P<0.001). Semi-quantitative RT-PCR and Western blotting showed that NSCLC specimens had increased Gankyrin mRNA and protein expression compared to the corresponding normal tissues. Out of all the clinicopathological factors analyzed, Gankyrin overexpression was significantly correlated with lymphatic metastasis (P<0.001) and p-TNM stage (P<0.001). Gankyrin-overexpressed NSCLC patients had a significantly shorter survival time (P<0.001, Log-rank test), and the prognostic significance of Gankyrin overexpression was apparent in both squamous cell carcinoma patients (P=0.028) and adenocarcinoma patients (P<0.001). Multivariate analysis indicated that Gankyrin overexpression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.51; P=0.041). ConclusionOur results indicate that Gankyrin overexpression is of clinical significance and can serve as a prognostic biomarker in NSCLC.