{"title":"Prognostic and Immunological Significance of NMNAT1 in Colorectal and Pan-Cancer Contexts.","authors":"Liang Wen, Ping Wang, Guosheng Zhang, Yongli Ma, Jinghui Li, Dengzhuo Chen, Linfeng Liu, Hongkai Hu, Chengzhi Huang, Xueqing Yao","doi":"10.2147/OTT.S504668","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Nicotinamide plays a critical role in the prevention and treatment of tumors, and its metabolism is closely associated with tumor progression. The aim of this study was to understand the prognostic and immunological significance of nicotinamide metabolism-related genes in pan-cancer.</p><p><strong>Methods: </strong>We downloaded The Cancer Genome Atlas and Genotype Tissue Expression pan-cancer datasets for NMNAT1 from the UCSC database. We analyzed the differential expression, prognosis, genetic alterations, DNA methylation, immune infiltration, and co-expression with RNA modification-related genes and immune checkpoint-related genes. Genes with expression patterns similar to NMNAT1 were identified using the GEPIA library. The GSCA database was used to investigate the correlation between gene expression and drug sensitivity, as assessed by GDSC and CTRP. The CancerSEA database was employed to examine the association of NMNAT1 expression at the single-cell level across different tumors and its relation to 14 functional states. Immunohistochemistry was performed to assess the clinical significance of NMNAT1 expression.</p><p><strong>Results: </strong>NMNAT1 exhibited differential expression across 25 tumor types, including colorectal cancer (CRC), and its expression was significantly associated with the prognosis of 11 tumors. Furthermore, NMNAT1 expression correlated significantly with clinicopathological features. NMNAT1 was strongly associated with immune cells, RNA modification-related genes, and immune checkpoint-related genes in most tumors, affecting immune responses. The expression of NMNAT1 also correlated with sensitivity and resistance to several drugs. Single-cell analysis revealed that NMNAT1 is involved in the progression of retinoblastoma, uveal melanoma, and CRC. Immunohistochemical analysis confirmed that NMNAT1 expression is an independent prognostic factor in patients with CRC.</p><p><strong>Conclusion: </strong>NMNAT1 is a crucial prognostic and immune marker gene for nicotinamide metabolism, particularly in CRC. It has potential as a clinical biomarker and a therapeutic target for cancer treatment.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"389-410"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954486/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"OncoTargets and therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/OTT.S504668","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Nicotinamide plays a critical role in the prevention and treatment of tumors, and its metabolism is closely associated with tumor progression. The aim of this study was to understand the prognostic and immunological significance of nicotinamide metabolism-related genes in pan-cancer.
Methods: We downloaded The Cancer Genome Atlas and Genotype Tissue Expression pan-cancer datasets for NMNAT1 from the UCSC database. We analyzed the differential expression, prognosis, genetic alterations, DNA methylation, immune infiltration, and co-expression with RNA modification-related genes and immune checkpoint-related genes. Genes with expression patterns similar to NMNAT1 were identified using the GEPIA library. The GSCA database was used to investigate the correlation between gene expression and drug sensitivity, as assessed by GDSC and CTRP. The CancerSEA database was employed to examine the association of NMNAT1 expression at the single-cell level across different tumors and its relation to 14 functional states. Immunohistochemistry was performed to assess the clinical significance of NMNAT1 expression.
Results: NMNAT1 exhibited differential expression across 25 tumor types, including colorectal cancer (CRC), and its expression was significantly associated with the prognosis of 11 tumors. Furthermore, NMNAT1 expression correlated significantly with clinicopathological features. NMNAT1 was strongly associated with immune cells, RNA modification-related genes, and immune checkpoint-related genes in most tumors, affecting immune responses. The expression of NMNAT1 also correlated with sensitivity and resistance to several drugs. Single-cell analysis revealed that NMNAT1 is involved in the progression of retinoblastoma, uveal melanoma, and CRC. Immunohistochemical analysis confirmed that NMNAT1 expression is an independent prognostic factor in patients with CRC.
Conclusion: NMNAT1 is a crucial prognostic and immune marker gene for nicotinamide metabolism, particularly in CRC. It has potential as a clinical biomarker and a therapeutic target for cancer treatment.
期刊介绍:
OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer.
The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype.
Specific topics covered by the journal include:
-Novel therapeutic targets and innovative agents
-Novel therapeutic regimens for improved benefit and/or decreased side effects
-Early stage clinical trials
Further considerations when submitting to OncoTargets and Therapy:
-Studies containing in vivo animal model data will be considered favorably.
-Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines.
-Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples.
-Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Single nucleotide polymorphism (SNP) studies will not be considered.