Combined expression of protein disulfide isomerase and endoplasmic reticulum oxidoreductin 1-α is a poor prognostic marker for non-small cell lung cancer

Protein disulfide isomerase (PDI) is one of the most abundant proteins in the endoplasmic reticulum (ER) and is known as a primary ER resident target of cigarette smoke-induced oxidation. PDI dysfunction triggers unfolded protein response and ER stress. Endoplasmic reticulum oxidoreductin 1-alpha (ERO1A) is a major regulator of PDI, and recent evidence implicates PDI and ERO1A as tumor prognostic factors. However, the associated role of PDI and ERO1A and their prognostic impact in non-small cell lung cancers (NSCLCs) remains unknown. The present study investigated the expression of PDI and ERO1A using immunohistochemistry and examined its association with smoking status and their prognostic impact in 198 NSCLCs. PDI and ERO1A expression were observed in 71.2 and 69.2% of NSCLCs, respectively, and their expressions were significantly associated with each other (P<0.001). Individual PDI (P=0.001) and ERO1A (P=0.005) expression were significantly associated with shorter overall survival (OS) in univariate analysis. PDI expression was significantly associated with never smoking (P=0.003). PDI expression (P<0.001) and the co-expression of PDI and ERO1A (P<0.001) were independent poor prognostic factors for OS in patients with NSCLC in multivariate analysis. Individual expression and co-expression of PDI and ERO1A may be used as novel prognostic indicators of NSCLC outcome.