Wu Miaowei, Hu Weilei, Wang Guosheng, Yao Yihan, Yu Xiao-Fang
Cancer Institute, Second Affiliated Hospital, Cancer Institute, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Front Genet. 2020 Oct 28;11:580299. doi: 10.3389/fgene.2020.580299. eCollection 2020.
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.
胃癌（GC）是全球癌症相关死亡的第三大常见原因。免疫疗法是一种很有前景的癌症治疗方法。然而，尚不清楚哪种GC亚群将从免疫疗法中获益最大，因此有必要开发有效的生物标志物来预测免疫疗法的反应。烟酰胺N-甲基转移酶（NNMT）是癌症相关成纤维细胞（CAF）分化和癌症进展的代谢调节因子。在本研究中，我们在癌症基因组图谱胃腺癌STAD（TCGA-STAD）中探索了NNMT与肿瘤浸润免疫细胞（TIIC）和免疫标志物集的相关性。随后，我们筛选了与NNMT相关的基因并对这些基因进行了富集分析。我们最终使用连通性图谱（CMap）和比较毒理基因组学数据库（CTD）预测了19种最具潜力的小分子药物。此外，纳多洛尔、氨甲环酸、非布索坦和氨苯砜被认为是治疗GC最有前景的四种药物。总之，NNMT可作为反映免疫浸润水平的预后生物标志物和GC的新型治疗靶点。
