NAD(P)H:quinone oxidoreductase-1 overexpression predicts poor prognosis in small cell lung cancer.

Abstract

quinone oxidoreductase-1 (NQO1) is commonly elevated in various types of human cancers, including pancreatic, breast and thyroid cancer, as well as others. However, little is known concerning the status of NQO1 in small cell lung cancer (SCLC). To investigate the clinicopathological significance of NQO1 expression and evaluate its role as a potential prognostic marker in SCLC, protein and mRNA expression levels of NQO1 were determined in four fresh tissue samples of SCLC and paired adjacent non-cancerous tissues using western blotting and real-time qRT-PCR, respectively, and 115 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of NQO1 protein. The correlation between NQO1 expression and the clinicopathological features of SCLC was evaluated using the Chi-square (χ2) and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In regards to the results, levels of NQO1 protein and mRNA were significantly elevated in the four fresh tissue samples of SCLC compared with levels in the paired adjacent non-cancerous tissues, respectively. IHC analysis showed that the rate of strong positive NQO1 protein expression was significantly higher (48.70%) in SCLC when compared with the rate in either adjacent non-cancerous or normal lung tissues (both P<0.001). The rate of strong positive NQO1 protein expression was correlated with large tumor size (P=0.019), late pathologic stage (P=0.001) and the presence of lymph node metastasis (P=0.001). Moreover, high‑level expression of NQO1 protein was significantly correlated with lower disease-free survival (P=0.001) and 5-year survival rates (P<0.001) in SCLC patients, particularly early‑stage patients (P=0.045 and P=0.033, respectively). Further Cox analysis revealed that NQO1 expression emerged as a significantly independent hazard factor for the 5-year survival rate of patients with SCLC (P=0.042). In conclusion, NQO1 plays an important role in the progression of SCLC, and it may potentially be used as a biomarker and therapeutic target of SCLC.