Low expression of PDHA1 predicts poor prognosis in gastric cancer

PDH E1 component subunit alpha (PDHA1) has been reported to be biologically significant in several human tumors. The aim of this study was to investigate the expression of PDHA1 in gastric cancer (GC) and its relationship with clinicopathological characteristics and prognosis. Oncomine analysis of neoplastic vs. normal tissue showed that the mRNA levels of PDHA1 were significantly underexpressed in different types of GC across three analyses. Underexpression of PDHA1 was found in intestinal-type GC (P = 0.009), diffuse-type GC (P = 0.036), and mixed-type GC (P = 0.025). Immunohistochemical staining of the 174 GC tissue microarray showed that PDHA1 staining is much stronger in normal mucosa than in GC samples (P = 0.040). Furthermore, PDHA1 expression levels were found to be significantly lower in 69.05% (87/126) of poorly differentiated GCs as compared to the well or moderately differentiated ones (P = 0.037). Intriguingly, PDHA1 expression was significantly correlated with depth of invasion (P < 0.001), lymph node metastasis (P < 0.001), TNM stage (P < 0.001), and nerve invasion (P = 0.006). However, it was not correlated with gender, age, Lauren classification, and lymphovascular invasion (P > 0.05 for all). Kaplan-Meier analysis revealed that low tumor expression of PDHA1 was significantly correlated with a poorer overall survival in patients with GC (5-year overall survival rates for patients with low vs high PDHA1 expression = 49.8% vs 72.7%, hazard ratio of death from GC = 2.594, 95% CI = 1.527 to 4.408, P < 0.001). Multivariate analysis showed that PDHA1 (P = 0.025) was an independent predictor of overall survival. These findings are of potential clinical utility and merit further validation.