Dataset Information

NNMT Is an Immune-Related Prognostic Biomarker That Modulates the Tumor Microenvironment in Pan-Cancer.

ABSTRACT: Emerging evidence has revealed the significant roles of nicotinamide n-methyltransferase (NNMT) in cancer initiation, development, and progression; however, a pan-cancer analysis of NNMT has not been conducted. In this study, we first thoroughly investigated the expression and prognostic significance of NNMT and the relationship between NNMT and the tumor microenvironment using bioinformatic analysis. NNMT was significantly increased and associated with poor prognosis in many common cancers. NNMT expression correlated with the infiltration levels of cancer-associated fibroblasts and macrophages in pan-cancer. Function enrichment analysis discovered that NNMT related to cancer-promoting and immune pathways in various common cancers, such as colon adenocarcinoma, head and neck squamous cell carcinoma, ovarian serous cystadenocarcinoma, and stomach adenocarcinoma. NNMT expression was positively correlated with tumor-associated macrophages (TAMs), especially M2-like TAMs. The results suggest that NNMT might be a new biomarker for immune infiltration and poor prognosis in cancers, providing new direction on therapeutics of cancers.

SUBMITTER: Liu W

PROVIDER: S-EPMC9934984 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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NNMT Is an Immune-Related Prognostic Biomarker That Modulates the Tumor Microenvironment in Pan-Cancer.

Liu Wenxiu W Zhu Meng M Li Xiaoming X Er Limian L Li Shengmian S

Disease markers 20230209

Emerging evidence has revealed the significant roles of nicotinamide n-methyltransferase (NNMT) in cancer initiation, development, and progression; however, a pan-cancer analysis of NNMT has not been conducted. In this study, we first thoroughly investigated the expression and prognostic significance of NNMT and the relationship between NNMT and the tumor microenvironment using bioinformatic analysis. NNMT was significantly increased and associated with poor prognosis in many common cancers. NNM ...[more]

PMID: 36817086

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Project description:BackgroundThe role of HERV-H LTR-associating 2 (HHLA2) in cancer remains still unclear. This study analyzed the correlation between the prognosis and immune infiltrate function of HHLA2 in pan-cancers.MethodsHHLA2 expression in pan-cancers was analyzed using the databases of TCGA, GTEx, TIMER, GEPIA, UALCAN, and GSEA databases. Multiple bioinformatic methods were used to investigate the correlation of HHLA2 expression with survival, pathological stage, tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), immune cell infiltration, and immune checkpoint gene (ICG), and gene functional enrichment was performed by Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA).ResultsHHLA2 was aberrantly expressed and was strongly correlated with positive or negative prognosis in multiple human cancers, which revealed that HHLA2 might play a vital role during cancer formation and development. Kaplan-Meier (KM) curves across cancers revealed that HHLA2 expression was correlated with overall survival (OS) in eight cancers, disease-specific survival (DSS) in seven cancers, disease-free interval (DFI) in four cancers, and progression-free interval (PFI) in nine cancers. Furthermore, HHLA2 expression was positively correlated with TMB in 6 cancer types and negatively associated with TMB in 7 cancer types, respectively. The former included ESCA, HNSC, KIRP, PAAD, PRAD, and PCPG; the latter contained COAD, LGG, LUAD, LUSC, THYM, THCA, and UCEC. Additionally, we found HHLA2 expression was negatively related to MSI in ACC, COAD, PAAD, and UCEC. More importantly, HHLA2 expression was remarkably correlated with the degree of tumor-infiltrating immune in many cancers, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells and strongly associated with immune checkpoint genes in 13 tumor types. Furthermore, KEGG pathway analyses indicated that HHLA2 could potentially impact cancer etiology or pathogenesis by functioning in amino sugar and nucleotide sugar metabolism, cytosolic DNA sensing pathway, and peroxisome pathways. Meanwhile, GSVA analysis results all indicate that HHLA2 was correlated with TSC/mTOR, RTK, RAS/MAPK, PI3K/AKT, EMT, DNA Damage Response, Cell Cycle, and Apoptosis pathways in various cancers.ConclusionHHLA2 can function as a prognostic biomarker and correlate with tumor immunity in human pan-cancer due to its important role in tumorigenesis and immune infiltration, which provides new insight into developing new targeted treatments in cancers.

Project description:Tumor microenvironment (TME) is emerging as an essential part of cervical cancer (CC) tumorigenesis and development, becoming a hotspot of research these years. However, comprehending the specific composition of TME is still facing enormous challenges, especially the immune and stromal components. In this study, we downloaded the RNA-seq profiles and somatic mutation data of 309 CC cases from The Cancer Genome Atlas (TCGA) database, which were analyzed by integrative bioinformatical methods. Initially, ESTIMATE computational method was employed to calculate the amount of immune and stromal components. Then, based on the high- and low-immunity cohorts, we recognized the differentially expressed genes (DEGs) as well as the differentially mutated genes (DMGs). Additionally, we conducted an intersection analysis of DEGs and DMGs, ultimately determining an immune-related prognostic signature, GTPase, IMAP Family Member 4 (GIMAP4). Moreover, sequential analyses demonstrated that GIMAP4 was a protective factor in CC, positively correlated with the overall survival (OS) and negatively with distant metastasis. Besides, we utilized the Gene Set Enrichment Analysis (GSEA) to explore the enrichment-pathways in high and low-expression cohorts of GIMAP4. The results indicated that the genes of the high-expression cohort had a high enrichment in immune-related biological processes and metabolic activities in the low one. Furthermore, CIBERSORT analysis was applied to evaluate the proportion of tumor-infiltrating immune cells (TICs), illustrating that several activated TICs were strongly associated with GIMAP4 expression, which suggested that GIMAP4 had the potential to be an indicator for the immune state in TME of CC. Hence, GIMAP4 contributed to predicting the CC patients' clinical outcomes, such as survival rate, distant metastasis and immunotherapy response. Moreover, GIMAP4 could serve as a promising biomarker for TME remodeling, suggesting the possible underlying mechanisms of tumorigenesis and CC progression, which may provide different therapeutic perceptions of CC, and therefore improve treatment.

Dataset Information

NNMT Is an Immune-Related Prognostic Biomarker That Modulates the Tumor Microenvironment in Pan-Cancer.

Publications

NNMT Is an Immune-Related Prognostic Biomarker That Modulates the Tumor Microenvironment in Pan-Cancer.

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