Clinicopathological implications of NQO1 overexpression in the prognosis of pancreatic adenocarcinoma

Abstract

Nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1) protects cells from oxidative damage. NQO1 has been reported to be upregulated in numerous solid tumors, suggesting a role in carcinogenesis and tumor progression. The present study attempted to investigate the clinical prognostic significance of NQO1 overexpression in pancreatic ductal adenocarcinoma (PDAC). A total of 181 tissue specimens were studied, including 126 PDAC and 55 normal pancreas specimens, which were selected for immunohistochemical staining of NQO1 protein. Immunofluorescence staining was additionally performed to identify the subcellular localization of NQO1 protein in pancreatic cancer BxPC-3 cells. The association between NQO1 overexpression and the clinical features of PDAC were evaluated byχ2 and Fisher's exact test. Overall survival of PDAC patients was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The NQO1 protein was mainly located in the cytoplasm and nucleus of BxPC-3 cells. The strongly positive rate of NQO1 expression in PDAC (65.9%, 83/126) was increased compared with that in normal pancreatic tissues (10.9%, 6/55). The positive rate of NQO1 protein was associated with grading, lymph node stage and tumor-node-metastasis (TNM) stage. Additionally, multivariate analysis suggested that NQO1 was a significant independent prognostic factor along with TNM stage in PDAC. In conclusion, high expression of NQO1 appears to be associated with PDAC progression, and may be an independent prognostic biomarker in PDAC.