Abstract
Background: Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes N-methylation of pyridine-containing compounds. NNMT is upregulated in many types of solid tumors, suggesting the potential for its use as a tumor biomarker. However, the prognostic value of NNMT in solid tumors is still unclear. We therefore conducted a meta-analysis to investigate the association between NNMT expression and survival in patients with solid tumors.Methods: We focused on patients with solid tumors, using high NNMT expression levels as the intervention and low NNMT expression levels as the comparison, according to Patient, Intervention, Comparison, and Outcome (PICO) guidelines. Electronic databases (up to June 7, 2018) were comprehensively searched to collect relevant cohort studies regarding the associations between NNMT expression levels and survival outcomes (overall survival [OS], disease-specific survival [DSS] including cancer-specific survival [CSS], and time to tumor progression [TTP] including disease-free survival [DFS], progression-free survival [PFS], and metastasis-free survival [MeFS]). Publication biases were also examined. All analyses were performed using STATA 12.0 software.Results: A total of 3340 patients with solid tumors from nine published studies were included. The combined hazard ratio (HR) identified high NNMT expression levels as a poor prognostic predictor of OS (HR = 1.67, 95% CI = 1.23–2.26). However, NNMT levels had no significant association with DSS (HR = 1.47, 95% CI = 0.95–2.28) and TTP (HR = 1.13, 95%CI = 0.39–3.25).Conclusion: High NNMT expression levels may be a poor prognostic biomarker for patients with solid tumors.
Highlights
Cancer is one of the leading causes of morbidity and mortality worldwide
The combined hazard ratio (HR) identified high Nicotinamide Nmethyltransferase (NNMT) expression levels as a poor prognostic predictor of overall survival (OS) (HR = 1.67, 95% confidence interval (CI) = 1.23–2.26)
NNMT levels had no significant association with disease-specific survival (DSS) (HR = 1.47, 95% CI = 0.95–2.28) and to tumor progression (TTP) (HR = 1.13, 95%CI = 0.39–3.25)
Summary
Cancer is one of the leading causes of morbidity and mortality worldwide. In 2012, approximately 8.2 million deaths occurred due to cancer (Torre et al, 2015). Nicotinamide Nmethyltransferase (NNMT) is essential for histone methylation, and its expression results in dysregulated transcription and translation of several key genes involved in the development of glioblastoma. High NNMT expression levels correlate with poor prognosis in patients with glioblastoma (Jung et al, 2017), gastric cancer (Chen et al, 2016), and pancreatic cancer (Xu et al, 2016). Results obtained from these studies did not show a statistically significant correlation between NNMT levels and prognosis in patients with glioblastoma (Jung et al, 2017), pancreatic cancer (Bi et al, 2014), and lung cancer (Ujiie et al, 2012). We conducted a meta-analysis to investigate the association between NNMT expression and survival in patients with solid tumors
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