Clinical significance of NQO1 expression in KRAS wild-type colorectal cancer

NAD(P)H: quinone oxidoreductase-1 (NQO1) protects cells against redox cycling and oxidative stress; however, in cancer cells, NQO1 confers resistance against anticancer agents. The aim of this study was to evaluate the association between NQO1 expression and prognosis in patients with advanced (locally advanced or metastatic/recurrent) colorectal cancer (CRC). A retrospective analysis of 47 patients [28 male and 19 female. median age: 62 years (range, 17-78)] with advanced CRC was conducted. Immunohistochemical examination of tumor tissue specimens was performed using monoclonal anti-NQO1 antibody. The association of NQO1 expression with patient characteristics, chemotherapeutic response, and clinical prognosis was assessed. Therapeutic efficacy (complete response, partial response, stable disease, and progressive disease) was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. We compared the therapeutic efficacy in KRAS wild and mutant CRC because epidermal growth factor receptor (EGFR)-signaling pathway plays a pivotal role in CRC. Of the 47 patients, 31 (66.0%) had KRAS wild CRC and 16 (34.0%) had KRAS mutant CRC. Moreover, 37 (78.7%) had NQO1-positive tumors and 10 (21.3%) had NQO1-negative tumors. Among the patients with KRAS wild CRC, NQO1-negative patients showed significantly better disease control rate (complete response + partial response + stable disease) than NQO1-positive patients (P = 0.028). Moreover, NQO1-negative patients had longer progression-free survival and overall survival than NQO1-positive patients (P = 0.041 and P = 0.043, respectively). NQO1 expression in the tumor may be a predictor of therapeutic efficacy and prognosis in patients with KRAS wild advanced CRC.