Pyruvate dehydrogenase E1α represents a reliable prognostic predictor for patients with non-small cell lung cancer resected via curative operation

Abstract

Background: Lung cancer is associated with a high morbidity and mortality rate worldwide; however, no reliable and independent prognostic predictor for non-small cell lung cancer (NSCLC) after curative surgery is available. Glucose metabolism is correlated with cancer cell proliferation. Pyruvate dehydrogenase E1α (PDH-E1α) catalyzes the conversion of pyruvate to acetyl-CoA and promotes aerobic glucose metabolism.In this study, we examined the relationship between PDH-E1α expression and clinicopathological factors associated with NSCLC to identify a reliable prognostic predictor of NSCLC after curative surgery. Methods: A total of 445 patients with NSCLC who underwent curative resection were enrolled in this study. PDH-E1α expression was evaluated via immunohistochemistry. We analyzed the correlation between PDH-E1α expression and clinicopathological features of the patients. Results: In total, 248 (56%) of the 445 patients with NSCLC were PDH-E1α-positive, and 197 patients were PDH-E1α-negative. PDH-E1α positivity was significantly correlated with the presence of adenocarcinoma (P<0.001) compared to the PDH-E1α-negative group. Patients with NSCLC showing PDH-E1α-negative expression had a significantly poorer overall survival rate (P=0.007) than those showing PDH-E1α-positive expression, especially at stage II. Patients with PDH-E1α negative expression also showed a poorer disease-free survival rate (P=0.02). Multivariate analysis revealed that PDH-E1α negativity (P=0.037) and male sex (P<0.001) were significantly correlated with a poor overall survival.Conclusions: PDH-E1α may represent a reliable prognostic predictor for NSCLC in patients that have recently undergone curative resection, especially at stage II.