{"title":"脂肪酸代谢特征有助于对预后较差、突变负担较低的恶性胃癌亚型进行分子诊断","authors":"Zhengwei Chen, Guoxiong Cheng","doi":"10.2174/1574892819666230907145036","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a common gastrointestinal tumor with high morbidity and mortality. Fatty acid metabolism (FAM) contributes to GC development. Patents have been issued for the use of compositions comprising fatty acid analogues for the treatment of many clinical conditions. However, its clinical significance and its relationship with tumor-related mutations have not been thoroughly discovered. This study was conducted to analyze and explore FAM-related genes' molecular characteristics, prognostic significance, and association with tumor- related mutations.</p><p><strong>Methods: </strong>The gastric adenocarcinoma's transcriptome, clinical data, and tumor mutation load (TMB) data were downloaded from TCGA and GEO databases. The differentially expressed FAM genes (FAM DEGs) between cancer and control samples were screened, and their correlation with TMB and survival was analyzed. A PPI network of FAM DEGs was constructed, and a downscaling clustering analysis was performed based on the expression of the FAM DEGs. Further immuno- infiltration and GO/KEGG enrichment analyses of the identified FAM clusters were performed to explore their heterogeneity in biological functions. The effects of FAM score and gastric cancer (STAD) on TMB, MSI, survival prognosis, and drug sensitivity were jointly analyzed, and finally, a single-gene analysis of the obtained core targets was performed.</p><p><strong>Results: </strong>Through differential analysis, 68 FAM DEGs were obtained, and they were highly associated with STAD tumor mutation load. In addition, a high FAM DEGs CNV rate was observed. The PPI network showed a complex mutual correlation between the FAM DEGs. Consensus clustering classified the patients into three clusters based on the FAM DEGs, and the clusters presented different survival rates. The GSVA and immune infiltration analysis revealed that metabolism, apoptosis, and immune infiltration-related pathways were variated. In addition, FAM genes, STAD prognostic risk genes, and PCA scores were closely associated with the survival status of STAD patients. FAM score was closely correlated with STAD TMB, MSI, and immunotherapy, and the TMB values in the low FAM score group were significantly higher than those in the high FAM score group. Finally, combining the above results, it was found that the core gene PTGS1 performed best in predicting STAD survival prognosis and TMB/MSI/immunotherapy.</p><p><strong>Conclusion: </strong>Fatty acid metabolism genes affect the development of gastric adenocarcinoma and can predict the survival prognosis, tumor mutational load characteristics, and drug therapy sensitivity of STAD patients, which can help explore more effective immunotherapy targets for GC.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"666-680"},"PeriodicalIF":2.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fatty Acid Metabolism Signature Contributes to the Molecular Diagnosis of a Malignant Gastric Cancer Subtype with Poor Prognosis and Lower Mutation Burden.\",\"authors\":\"Zhengwei Chen, Guoxiong Cheng\",\"doi\":\"10.2174/1574892819666230907145036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gastric cancer (GC) is a common gastrointestinal tumor with high morbidity and mortality. Fatty acid metabolism (FAM) contributes to GC development. Patents have been issued for the use of compositions comprising fatty acid analogues for the treatment of many clinical conditions. However, its clinical significance and its relationship with tumor-related mutations have not been thoroughly discovered. This study was conducted to analyze and explore FAM-related genes' molecular characteristics, prognostic significance, and association with tumor- related mutations.</p><p><strong>Methods: </strong>The gastric adenocarcinoma's transcriptome, clinical data, and tumor mutation load (TMB) data were downloaded from TCGA and GEO databases. The differentially expressed FAM genes (FAM DEGs) between cancer and control samples were screened, and their correlation with TMB and survival was analyzed. A PPI network of FAM DEGs was constructed, and a downscaling clustering analysis was performed based on the expression of the FAM DEGs. Further immuno- infiltration and GO/KEGG enrichment analyses of the identified FAM clusters were performed to explore their heterogeneity in biological functions. The effects of FAM score and gastric cancer (STAD) on TMB, MSI, survival prognosis, and drug sensitivity were jointly analyzed, and finally, a single-gene analysis of the obtained core targets was performed.</p><p><strong>Results: </strong>Through differential analysis, 68 FAM DEGs were obtained, and they were highly associated with STAD tumor mutation load. In addition, a high FAM DEGs CNV rate was observed. The PPI network showed a complex mutual correlation between the FAM DEGs. Consensus clustering classified the patients into three clusters based on the FAM DEGs, and the clusters presented different survival rates. The GSVA and immune infiltration analysis revealed that metabolism, apoptosis, and immune infiltration-related pathways were variated. In addition, FAM genes, STAD prognostic risk genes, and PCA scores were closely associated with the survival status of STAD patients. FAM score was closely correlated with STAD TMB, MSI, and immunotherapy, and the TMB values in the low FAM score group were significantly higher than those in the high FAM score group. Finally, combining the above results, it was found that the core gene PTGS1 performed best in predicting STAD survival prognosis and TMB/MSI/immunotherapy.</p><p><strong>Conclusion: </strong>Fatty acid metabolism genes affect the development of gastric adenocarcinoma and can predict the survival prognosis, tumor mutational load characteristics, and drug therapy sensitivity of STAD patients, which can help explore more effective immunotherapy targets for GC.</p>\",\"PeriodicalId\":20774,\"journal\":{\"name\":\"Recent patents on anti-cancer drug discovery\",\"volume\":\" \",\"pages\":\"666-680\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Recent patents on anti-cancer drug discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1574892819666230907145036\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Recent patents on anti-cancer drug discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1574892819666230907145036","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Fatty Acid Metabolism Signature Contributes to the Molecular Diagnosis of a Malignant Gastric Cancer Subtype with Poor Prognosis and Lower Mutation Burden.
Background: Gastric cancer (GC) is a common gastrointestinal tumor with high morbidity and mortality. Fatty acid metabolism (FAM) contributes to GC development. Patents have been issued for the use of compositions comprising fatty acid analogues for the treatment of many clinical conditions. However, its clinical significance and its relationship with tumor-related mutations have not been thoroughly discovered. This study was conducted to analyze and explore FAM-related genes' molecular characteristics, prognostic significance, and association with tumor- related mutations.
Methods: The gastric adenocarcinoma's transcriptome, clinical data, and tumor mutation load (TMB) data were downloaded from TCGA and GEO databases. The differentially expressed FAM genes (FAM DEGs) between cancer and control samples were screened, and their correlation with TMB and survival was analyzed. A PPI network of FAM DEGs was constructed, and a downscaling clustering analysis was performed based on the expression of the FAM DEGs. Further immuno- infiltration and GO/KEGG enrichment analyses of the identified FAM clusters were performed to explore their heterogeneity in biological functions. The effects of FAM score and gastric cancer (STAD) on TMB, MSI, survival prognosis, and drug sensitivity were jointly analyzed, and finally, a single-gene analysis of the obtained core targets was performed.
Results: Through differential analysis, 68 FAM DEGs were obtained, and they were highly associated with STAD tumor mutation load. In addition, a high FAM DEGs CNV rate was observed. The PPI network showed a complex mutual correlation between the FAM DEGs. Consensus clustering classified the patients into three clusters based on the FAM DEGs, and the clusters presented different survival rates. The GSVA and immune infiltration analysis revealed that metabolism, apoptosis, and immune infiltration-related pathways were variated. In addition, FAM genes, STAD prognostic risk genes, and PCA scores were closely associated with the survival status of STAD patients. FAM score was closely correlated with STAD TMB, MSI, and immunotherapy, and the TMB values in the low FAM score group were significantly higher than those in the high FAM score group. Finally, combining the above results, it was found that the core gene PTGS1 performed best in predicting STAD survival prognosis and TMB/MSI/immunotherapy.
Conclusion: Fatty acid metabolism genes affect the development of gastric adenocarcinoma and can predict the survival prognosis, tumor mutational load characteristics, and drug therapy sensitivity of STAD patients, which can help explore more effective immunotherapy targets for GC.
期刊介绍:
Aims & Scope
Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.