Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer
BackgroundCholesterol metabolism plays a crucial role in tumor progression and immune response modulation. However, the precise connection between cholesterol metabolism-related genes (CMRGs) and their implications for clinical prognosis, the tumor microenvironment (TME), and the outcomes of immunot...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1518010/full |
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| author | Chengjun Zhu Chengjun Zhu Mengpei Yan Mengpei Yan Zhijun Zhang Zhijun Zhang Yikai Shen Yikai Shen Wangwen Wang Zetian Chen Zetian Chen Changsheng Cai Changsheng Cai Hongda Liu Hongda Liu Zekuan Xu Zekuan Xu Zekuan Xu Zekuan Xu Zheng Li Zheng Li |
| author_facet | Chengjun Zhu Chengjun Zhu Mengpei Yan Mengpei Yan Zhijun Zhang Zhijun Zhang Yikai Shen Yikai Shen Wangwen Wang Zetian Chen Zetian Chen Changsheng Cai Changsheng Cai Hongda Liu Hongda Liu Zekuan Xu Zekuan Xu Zekuan Xu Zekuan Xu Zheng Li Zheng Li |
| author_sort | Chengjun Zhu |
| collection | DOAJ |
| description | BackgroundCholesterol metabolism plays a crucial role in tumor progression and immune response modulation. However, the precise connection between cholesterol metabolism-related genes (CMRGs) and their implications for clinical prognosis, the tumor microenvironment (TME), and the outcomes of immunotherapy in gastric cancer remains to be fully elucidated.MethodsTranscriptome data and related clinical information from 675 gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 50 cholesterol metabolism-related genes (CMRGs) were identified from the Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04979). Consensus clustering analysis was used to classify patients into distinct molecular subgroups, while principal component analysis (PCA) was applied to develop a prognostic scoring system for predicting survival and immunotherapy response. The scoring system was validated using three independent cohorts of gastric cancer patients.ResultsBased on 49 CMRGs, 675 gastric cancer patients were categorized into three distinct subgroups with varying prognoses, tumor microenvironment features, and clinical characteristics. Further differential gene analysis and consensus clustering identified two additional subgroups. The prognostic scoring system developed through PCA demonstrated that the high-score subgroup had significantly improved survival, higher tumor mutational burden (TMB), and microsatellite instability (MSI), as well as a greater number of mutated genes, indicating greater sensitivity to immunotherapy. This system was validated in a real-world cohort undergoing immunotherapy. Additionally, the correlation between GPC3 expression and cholesterol levels was confirmed, highlighting GPC3’s potential biological role.ConclusionThis study highlights the importance of CMRGs in gastric cancer, deepens our understanding of the tumor immune microenvironment, and guides individualized immunotherapy. |
| format | Article |
| id | doaj-art-355c83807d364c32b2c55d1d8657c0e6 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-355c83807d364c32b2c55d1d8657c0e62024-12-24T05:10:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-12-011410.3389/fonc.2024.15180101518010Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancerChengjun Zhu0Chengjun Zhu1Mengpei Yan2Mengpei Yan3Zhijun Zhang4Zhijun Zhang5Yikai Shen6Yikai Shen7Wangwen Wang8Zetian Chen9Zetian Chen10Changsheng Cai11Changsheng Cai12Hongda Liu13Hongda Liu14Zekuan Xu15Zekuan Xu16Zekuan Xu17Zekuan Xu18Zheng Li19Zheng Li20Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Geriatric Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaCollaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaThe Institute of Gastric Cancer, Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaGastric Cancer Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackgroundCholesterol metabolism plays a crucial role in tumor progression and immune response modulation. However, the precise connection between cholesterol metabolism-related genes (CMRGs) and their implications for clinical prognosis, the tumor microenvironment (TME), and the outcomes of immunotherapy in gastric cancer remains to be fully elucidated.MethodsTranscriptome data and related clinical information from 675 gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 50 cholesterol metabolism-related genes (CMRGs) were identified from the Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04979). Consensus clustering analysis was used to classify patients into distinct molecular subgroups, while principal component analysis (PCA) was applied to develop a prognostic scoring system for predicting survival and immunotherapy response. The scoring system was validated using three independent cohorts of gastric cancer patients.ResultsBased on 49 CMRGs, 675 gastric cancer patients were categorized into three distinct subgroups with varying prognoses, tumor microenvironment features, and clinical characteristics. Further differential gene analysis and consensus clustering identified two additional subgroups. The prognostic scoring system developed through PCA demonstrated that the high-score subgroup had significantly improved survival, higher tumor mutational burden (TMB), and microsatellite instability (MSI), as well as a greater number of mutated genes, indicating greater sensitivity to immunotherapy. This system was validated in a real-world cohort undergoing immunotherapy. Additionally, the correlation between GPC3 expression and cholesterol levels was confirmed, highlighting GPC3’s potential biological role.ConclusionThis study highlights the importance of CMRGs in gastric cancer, deepens our understanding of the tumor immune microenvironment, and guides individualized immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2024.1518010/fullgastric cancercholesterolprognosistumor microenvironmentimmunotherapy |
| spellingShingle | Chengjun Zhu Chengjun Zhu Mengpei Yan Mengpei Yan Zhijun Zhang Zhijun Zhang Yikai Shen Yikai Shen Wangwen Wang Zetian Chen Zetian Chen Changsheng Cai Changsheng Cai Hongda Liu Hongda Liu Zekuan Xu Zekuan Xu Zekuan Xu Zekuan Xu Zheng Li Zheng Li Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer Frontiers in Oncology gastric cancer cholesterol prognosis tumor microenvironment immunotherapy |
| title | Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer |
| title_full | Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer |
| title_fullStr | Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer |
| title_full_unstemmed | Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer |
| title_short | Prediction of prognosis, immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer |
| title_sort | prediction of prognosis immunogenicity and efficacy of immunotherapy based on cholesterol metabolism in gastric cancer |
| topic | gastric cancer cholesterol prognosis tumor microenvironment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1518010/full |
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