Abstract
Gastric cancer (GC) is the third most common cause of cancer-related death in the word. Immunotherapy is a promising treatment of cancer. However, it is unclear which GC subpopulation would benefit most from immunotherapy and it is necessary to develop effective biomarkers for predicting immunotherapy response. Nicotinamide N-methyltransferase (NNMT) is a metabolic regulator of cancer-associated fibroblast (CAF) differentiation and cancer progression. In this study, we explored the correlations of NNMT to tumor-infiltrating immune cells (TIICs) and immune marker sets in The Cancer Genome Atlas Stomach Adenocarcinoma STAD (TCGA-STAD). Subsequently, we screened the NNMT correlated genes and performed the enrichment analysis of these genes. We eventually predicted the 19 most potential small-molecule drugs using the connectivity map (CMap) and Comparative Toxicogenomics Database (CTD). Also, nadolol, tranexamic acid, felbinac and dapsone were considered the four most promising drugs for GC. In summary, NNMT can be used as a prognostic biomarker that reflect immune infiltration level and a novel therapeutic target in GC.
Highlights
Gastric cancer (GC) is the third leading cause of death by cancer worldwide (Bray et al, 2018)
We found that Nicotinamide N-methyltransferase (NNMT) expression was significantly negatively associated with the infiltration level of B
Our results showed that a high level of NNMT was related to longer survival in HER2-negative GC patients who received 5-FU-based adjuvant chemotherapy, suggesting that NNMT could be an indicator of successful 5-FU treatment in GC
Summary
Gastric cancer (GC) is the third leading cause of death by cancer worldwide (Bray et al, 2018). The disease is often diagnosed during its advanced stages, leading to the high mortality for GC patients (Digklia and Wagner, 2016). Knowing more about the molecular mechanisms contributing to GC progression can help us develop more effective treatment regimens. As we have come to appreciate the importance of tumor-associated immune mechanisms in GC, immunotherapy has become a standard of treatment for many solid tumors (Larkin et al, 2019; Mok et al, 2019), but not yet for gastrointestinal cancers (Pagni et al, 2019). Immune checkpoint blockade with antibodies targeting cytotoxic CTLA-4, PD-1, and PD-L1 has shown clinical activity in some GC patients, it is still unclear which GC subpopulation would benefit most from checkpoint inhibitors (Magalhaes et al, 2018), since PD-L1 immunohistochemistry
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