Prognostic Value of Inducible Nitric Oxide Synthase (iNOS) in Human Cancer: A Systematic Review and Meta-Analysis

BACKGROUND: Inducible nitric oxide synthase (iNOS) is confirmed to regulate the production of nitric oxide (NO) when cells are exposed to external stimulus. Recent publications revealed that overexpression of iNOS predicted poor clinical outcomes for patients with malignant cancers, e.g., gastric, bladder, and colorectal cancers; however, several studies reported no obvious relationship between iNOS expression and prognosis of solid tumors. The aim of our study was to investigate the pooled effect of the prognostic value of iNOS expression. MATERIALS AND METHODS: We performed a systematic search of PubMed, Web of Science, and Embase databases up to January 15, 2019. The concerned outcomes of interest included overall survival (OS), cancer-special survival (CSS), and recurrence-free survival (RFS). RESULTS: Fourteen studies with 1,758 patients were included in this meta-analysis, and we reached the conclusion that increased iNOS expression was significantly associated with worse OS (HR: 1.89, 95% CI: 1.57 - 2.28, p ≤ 0.001), worse CSS (HR: 3.13, 95% CI: 1.88 - 5.20, p ≤ 0.001), and worse RFS (HR: 2.16, 95% CI: 1.29 - 3.62, p = 0.003) in solid tumors. Furthermore, the subgroup analysis identified the significant relationship of high iNOS expression with poor OS in gastric cancer. No obvious publication bias was detected by Begg's tests. CONCLUSION: In summary, the results drawn in our meta-analysis demonstrated that elevated expression of iNOS had a significant association with poor survival in human cancer. iNOS might serve as a promising predictive biomarker of prognosis in cancer patients, and well-designed prospective studies are further needed to substantiate the prognostic value of iNOS.