Abstract

BackgroundPrevious studies indicated that dysregulated expression of nicotinamide N-methyltransferase (NNMT) contributed to the tumor progression and predicted poor prognosis in various cancers. However, there was no exact conclusion on account of the contradictory results across studies.MethodsThe relevant studies up to December 7, 2020 were searched in PubMed, Web of Science, and Embase. The association between NNMT expression and prognostic outcomes was explored, including overall survival (OS), disease-free survival (DFS), and clinicopathological features. The bioinformatics database was used to validate the findings.ResultsThirteen retrospective studies containing 2,591 patients with cancers were included in this analysis. High NNMT expression was significantly associated with shorter OS (hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.42–2.86, and P < 0.01) and DFS (HR = 1.59, 95% CI = 1.23–2.05, and P < 0.01) compared to low NNMT expression in cancers. Compared to patients with low NNMT expression, patients with high NNMT expression tended to have worse tumor differentiation (P = 0.03), earlier lymph node metastasis (P = 0.01), earlier distant metastasis (P = 0.02), and more advanced clinical stage (P < 0.01).ConclusionHigh NNMT expression is an unfavorable factor of various cancers. NNMT is a promising indicator to predict the prognosis of various cancers and can serve as a potential therapeutic target in various cancers.

Highlights

  • Cancer has become one of the major public health concerns globally and the leading cause of death [1]

  • Inclusion criteria for selecting the studies were as follows: (1) patients were diagnosed with any type of cancer; (2) studies explored the association of Nicotinamide N-methyltransferase (NNMT) expression with clinicopathological parameters (CP) and survival outcomes of cancer patients, such as overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and recurrence-free survival (RFS); (3) studies had the retrospective or prospective design; and (4) studies were published in English

  • Recent studies have showed that NNMT expression played an important role in the tumor progression and might induce an unfavorable survival outcome for cancer patients, definite conclusion has not been obtained for small sample size and contradictory results of existing evidence [9,10,11,12,13,14,15,16,17,18,19,20,21]

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Summary

Introduction

Cancer has become one of the major public health concerns globally and the leading cause of death [1]. Despite the great improvement in diagnosis and treatment, many patients suffered from a poor prognosis, especially those at advanced clinical stage [1] To solve this dilemma, increasing number of researchers are devoted to establishing new potential biomarkers to improve the clinical decision-making and prolong the survival time of cancer patients [3,4]. Definite conclusion about the prognostic value of NNMT expression in human cancers has not been determined on account of contradictory results among existing evidence [9,10,11,12,13,14,15,16,17,18,19,20,21]. Chen et al found that overexpression of NNMT might predict the shorter survival time (P = 0.03) and be associated with worse clinicopathological features (e.g., distant metastasis and clinical stage) in gastric cancer [11]. We performed this meta-analysis by integrating the existing evidence and validated our findings using the bioinformatics database

Literature search
Database validation
Study inclusion and exclusion criteria
Statistical analysis
Literature search and selection
Characteristics of included studies
Association between NNMT expression and OS
Association between NNMT expression and DFS
Association between NNMT expression and CP
Sensitivity analysis
Discussion
Conclusion

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