Association between F-18-FDG uptake in PET/CT, Nrf2 and NQO1 expression and their prognostic significance in non-small cell lung cancer

Abstract

Two pentose phosphate pathway-related proteins, NF-E2-related factor 2 (Nrf2)/NAD(P)H dehydrogenase (Quinone) 1 (NQO1) regulate the expression of glucose metabolism and antioxidant genes. We evaluated the prognostic significance of NRF2, NQO1 and F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG PET) parameter and their relationship with non-small cell lung cancer (NSCLC) histology. A total of 241 patients, who underwent surgical resection for NSCLC, were reviewed retrospectively. Preoperative F-18-FDG PET and immunohistochemical results of Nrf2 and NQO1 were evaluated. In squamous cell carcinoma (SQCC), the maximum standardized uptake value (SUVmax) was significantly higher in NQO1-high than in NQO1-low expression (p=0.023). In adenocarcinoma, SUVmax was not correlated with NQO1 expression. Patients with a high NQO1 expression showed poor recurrence-free survival (RFS) and overall survival (OS) than patients with a low NQO1 expression in SQCC (p=0.002 and p=0.014, respectively). NQO1 expression was not associated with clinical outcome in adenocarcinoma. Nrf2 expression was not correlated with prognosis in two types of NSCLC. High SUVmax was associated with poor RFS (p=0.03) but was not related to poor OS (p=0.569) in SQCC. In multivariate analyses, NQO1 expression and SUVmax were not independent prognostic factors in SQCC. However, in multivariate analysis combining NQO1 and SUVmax values, both low SUVmax and low NQO1 was independent prognostic factor for RFS and OS (HR=0.264, p=0.033 and HR=0.338, p=0.045, respectively). In conclusion, both low SUVmax and low NQO1 was an independent prognostic factor in SQCC alone. The sample size was small but there was a positive correlation between NQO1 expression and SUVmax in SQCC.