{"title":"Identification of Lung Adenocarcinoma Subtypes Based on Nicotinamide Metabolism-Related Genes to Assess Prognosis and Immunotherapy.","authors":"Meijun Peng, Qiuli Ding","doi":"10.1615/JEnvironPatholToxicolOncol.2025054052","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most malignant tumors with significant implications for population health and life. Nicotinamide metabolism may play a pivotal part in influencing the prognosis of LUAD. This study aimed to figure out the potential value of nicotinamide metabolism-related genes (NMRGs) in LUAD prognosis.</p><p><strong>Methods: </strong>Forty-two NMRGs were obtained from the Molecular Signatures Database and intersected with differentially expressed genes (DEGs) in LUAD from The Cancer Genome Atlas. Unsupervised consensus clustering was conducted based on the intersecting genes, followed by identification of DEGs between clusters. Enrichment analyses and LASSO-Cox regression analyses were conducted. Immune cell infiltration was calculated using the ssGSEA algorithm. Wilcoxon test was conducted on the TIDE scores of different risk groups. Targeted small molecule drug prediction was performed on the DEGs in groups.</p><p><strong>Results: </strong>A total of 10 nicotinamide metabolism-related differentially expressed genes (NMRDEGs) were identified for LUAD clustering. LUAD patients were divided into two clusters. Cluster 1 had considerably higher overall survival rates compared to cluster 2. Differential genes between clusters were mainly enriched in hormone metabolic processes and the neuroactive ligand-receptor interaction pathway. An 11-gene prognostic model was established to predict the overall survival of LUAD patients. The validation set showed that the model had a good prognostic effect. Analysis of immune cell infiltration demonstrated that in the high-risk (HR) group, infiltration levels of mast cells and neutrophils were considerably lower than low-risk (LR) group, while infiltration levels of NK cells and Th2 cells were considerably higher than LR group. TIDE scores indicated a lower likelihood of immune evasion and a potentially better response to immunotherapy in LR patients. Drug prediction showed that FGIN-1-43, deferiprone, and griseofulvin were potential drugs.</p><p><strong>Conclusion: </strong>We successfully developed a predictive model for the survival and immunotherapy response of LUAD patients.</p>","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"44 4","pages":"47-61"},"PeriodicalIF":2.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2025054052","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Background: Lung adenocarcinoma (LUAD) is one of the most malignant tumors with significant implications for population health and life. Nicotinamide metabolism may play a pivotal part in influencing the prognosis of LUAD. This study aimed to figure out the potential value of nicotinamide metabolism-related genes (NMRGs) in LUAD prognosis.
Methods: Forty-two NMRGs were obtained from the Molecular Signatures Database and intersected with differentially expressed genes (DEGs) in LUAD from The Cancer Genome Atlas. Unsupervised consensus clustering was conducted based on the intersecting genes, followed by identification of DEGs between clusters. Enrichment analyses and LASSO-Cox regression analyses were conducted. Immune cell infiltration was calculated using the ssGSEA algorithm. Wilcoxon test was conducted on the TIDE scores of different risk groups. Targeted small molecule drug prediction was performed on the DEGs in groups.
Results: A total of 10 nicotinamide metabolism-related differentially expressed genes (NMRDEGs) were identified for LUAD clustering. LUAD patients were divided into two clusters. Cluster 1 had considerably higher overall survival rates compared to cluster 2. Differential genes between clusters were mainly enriched in hormone metabolic processes and the neuroactive ligand-receptor interaction pathway. An 11-gene prognostic model was established to predict the overall survival of LUAD patients. The validation set showed that the model had a good prognostic effect. Analysis of immune cell infiltration demonstrated that in the high-risk (HR) group, infiltration levels of mast cells and neutrophils were considerably lower than low-risk (LR) group, while infiltration levels of NK cells and Th2 cells were considerably higher than LR group. TIDE scores indicated a lower likelihood of immune evasion and a potentially better response to immunotherapy in LR patients. Drug prediction showed that FGIN-1-43, deferiprone, and griseofulvin were potential drugs.
Conclusion: We successfully developed a predictive model for the survival and immunotherapy response of LUAD patients.
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