Significance of NQO1 overexpression for prognostic evaluation of gastric adenocarcinoma

摘要

NQO1 (NAD(P)H: quinone oxidoreductase, also known as DT-diaphorase) plays a prominent role in maintaining cellular homeostasis. NQO1 is abnormally elevated in many solid cancer types, including those of the adrenal gland, breast, colon, lung, ovary, and thyroid. However, little is known about the status of NQO1 in gastric adenocarcinoma (GAC). To investigate the clinicopathological significance of NQO1 expression in GAC, and thus evaluate its role as a potential prognostic marker, 203 cases of primary GAC, 31 of gastric dysplasia, and 53 of adjacent non-tumor tissues were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological characteristics were evaluated by χ2 test and Fisher's exact test, while survival rates were calculated by Kaplan-Meier method. The relationship between prognostic factors and patient survival was analyzed by Cox proportional hazards model.Through these analyses it was found that the strongly positive rate of NQO1 protein in GAC was significantly higher than that in gastric dysplasia and adjacent non-tumor tissues. Analysis by qRT-PCR also confirmed that NQO1 mRNA levels were increased in GAC compared with those detected in either adjacent non-tumor tissues or normal gastric mucosa. Additionally, the NQO1 expression rate was positively correlated with tumor size, serosal invasion, tumor stage, and both disease-free survival and 5-year survival rates. Further analysis showed that although NQO1 was not an independent predictor of GAC, elevated expression of NQO1 could predict lower disease-free survival and 5-year survival times in late-stage patients. In conclusion, NQO1 plays an important role in the progression of GAC, and might be a potential, but not an independent, poor prognostic biomarker and therapeutic target of GAC.