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Nicotinamide N-Methyltransferase Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer.

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.

SUBMITTER: Wu M

PROVIDER: S-EPMC7655872 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Nicotinamide N-Methyltransferase Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer.

Wu Miaowei M Hu Weilei W Wang Guosheng G Yao Yihan Y Yu Xiao-Fang XF

Frontiers in genetics 20201028

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 ...[more]

PMID: 33193702

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Project description:PurposeThe serine protease inhibitor clade E member 1 (SERPINE1) has been studied as a potential biomarker in a variety of cancers, but poorly studied in gastric cancer (GC). The purpose of this study was to explore the prognostic value of SERPINE1 in GC and primarily analyze its functions.MethodsWe analyzed the the prognostic value of SERPINE1 and studied the relationship with clinicopathologic biomarkers in gastric cancer. The expression of SERPINE1 was analyzed by GEO and TCGA databases. Moreover, we validated the results by immunohistochemistry. Next, the correlation analysis between SERPINE1 and the cuproptosis-related genes was analyzed by the "Spearman" method. CIBERSORT and TIMER algorithms were used to analyze the correlation of SERPINE1 with immune infiltration. Furthermore, GO and KEGG gene enrichment analyses were used to study the functions and pathways that SERPINE1 might be involved in. Then, drug sensitivity analysis was performed using CellMiner database. Finally, a cuproptosis-immune-related prognostic model was constructed using genes related to immune and cuproptosis, and verified against external datasets.ResultsSERPINE1 was up-regulated in gastric cancer tissues, which tends toward poor prognosis. Using immunohistochemistry experiment, the expression and prognostic value of SERPINE1 were verified. Then, we found that SERPINE1 was negatively correlated with cuproptosis-related genes FDX1, LIAS, LIPT1, and PDHA1. On the contrary, SERPINE1 was positively correlated with APOE. This indicates the effect of SERPINE1 on the cuproptosis process. Furthermore, by conducting immune-related analyses, it was revealed that SERPINE1 may promote the inhibitory immune microenvironment. The infiltration level of resting NK cells, neutrophils, activated mast cells, and macrophages M2 was positively correlated with SERPINE1. However, B cell memory and plasma cells were negatively correlated with SERPINE1. Functional analysis showed that SERPINE1 was closely related to angiogenesis, apoptosis, and ECM degradation. The KEGG pathway analysis showed that SERPINE1 may be associated with P53, Pi3k/Akt, TGF-β, and other signaling pathways. Drug sensitivity analysis showed that SERPINE1 could be also seen as a potential treatment target. The risk model based on SERPINE1 co-expression genes could better predict the survival of GC patients than SERPINE1 alone. We also verified the prognostic value of the risk score by GEO external datasets.ConclusionSERPINE1 is highly expressed in gastric cancer and related to poor prognosis. SERPINE1 may regulate cuproptosis and the immune microenvironment by a series of pathways. Therefore, SERPINE1 as a prognostic biomarker and potential therapeutic target deserves further study.

Dataset Information

Nicotinamide N-Methyltransferase Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer.

Publications

Nicotinamide N-Methyltransferase Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer.

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