Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer
BackgroundGlycerolipid metabolism is involved in the genesis and progression of colon cancer. The current study aims at exploring the prognostic value and potential molecular mechanism of glycerolipid metabolism-related genes in colon cancer from the perspective of multi-omics.MethodsClinical inform...
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| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.881953/full |
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| author | Zhiyu Wang Zhuoqi Zhang Ke Zhang Qiaoxia Zhou Sidong Chen Hao Zheng Guoqiang Wang Shangli Cai Fujing Wang Shenglong Li |
| author_facet | Zhiyu Wang Zhuoqi Zhang Ke Zhang Qiaoxia Zhou Sidong Chen Hao Zheng Guoqiang Wang Shangli Cai Fujing Wang Shenglong Li |
| author_sort | Zhiyu Wang |
| collection | DOAJ |
| description | BackgroundGlycerolipid metabolism is involved in the genesis and progression of colon cancer. The current study aims at exploring the prognostic value and potential molecular mechanism of glycerolipid metabolism-related genes in colon cancer from the perspective of multi-omics.MethodsClinical information and mRNA expression data of patients with colon cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the glycerolipid metabolism-related gene enrichment score (GLMS). Univariable and multivariable Cox regression analyses were used to study the prognostic value of GLMS in TCGA-COAD and GSE39582 cohorts. The molecular mechanism of the prognostic factor was investigated via immune cell infiltration estimation and correlation analysis of cancer hallmark pathways. Single-cell transcriptomic dataset GSE146771 was used to identify the cell populations which glycerolipid metabolism targeted on.ResultsThe GLMS was found to be associated with tumor location and consensus molecular types (CMSs) of colon cancer in TCGA-COAD cohort (P < 0.05). Patients in the low-GLMS group exhibited poorer overall survival (OS) in TCGA cohort (P = 0.03; HR, 0.63; 95% CI, 0.42–0.94), which was further validated in the GSE39582 dataset (P < 0.001; HR, 0.57; 95% CI, 0.43–0.76). The association between the GLMS and OS remained significant in the multivariable analysis (TCGA cohort: P = 0.04; HR, 0.64; 95% CI, 0.42–0.98; GSE39582 cohort: P < 0.001; HR, 0.60; 95% CI, 0.45–0.80). The GLMS was positively correlated with cancer hallmark pathways including bile acid metabolism, xenobiotic metabolism, and peroxisome and negatively correlated with pathways such as interferon gamma response, allograft rejection, apoptosis, and inflammatory response (P < 0.05). Increased immune infiltration and upregulated expression of immune checkpoints were observed in patients with lower GLMS (P < 0.05). Single-cell datasets verified the different distribution of GLMS in cell subsets, with significant enrichment of GLMS in malignant cells and Tprolif cells.ConclusionWe demonstrated that GLMS was a potential independent prognostic factor for colon cancer. The GLMS was also correlated with several cancer hallmark pathways, as well as immune microenvironment. |
| first_indexed | 2024-12-12T21:01:16Z |
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| id | doaj.art-8aa9ffdcfffe4e21af2acedc349c84cb |
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| language | English |
| last_indexed | 2024-12-12T21:01:16Z |
| publishDate | 2022-05-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-8aa9ffdcfffe4e21af2acedc349c84cb2022-12-22T00:12:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.881953881953Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon CancerZhiyu Wang0Zhuoqi Zhang1Ke Zhang2Qiaoxia Zhou3Sidong Chen4Hao Zheng5Guoqiang Wang6Shangli Cai7Fujing Wang8Shenglong Li9Department of Medical Oncology, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, ChinaDepartment of Gastrointestinal Surgery, Affiliated Hospital of Hebei University, Baoding, ChinaGeneral Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaMedical Department, Burning Rock Biotech, Guangzhou, ChinaMedical Department, Burning Rock Biotech, Guangzhou, ChinaGeneral Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaMedical Department, Burning Rock Biotech, Guangzhou, ChinaMedical Department, Burning Rock Biotech, Guangzhou, ChinaGeneral Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaGeneral Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackgroundGlycerolipid metabolism is involved in the genesis and progression of colon cancer. The current study aims at exploring the prognostic value and potential molecular mechanism of glycerolipid metabolism-related genes in colon cancer from the perspective of multi-omics.MethodsClinical information and mRNA expression data of patients with colon cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-sample gene set enrichment analysis (ssGSEA) was applied to calculate the glycerolipid metabolism-related gene enrichment score (GLMS). Univariable and multivariable Cox regression analyses were used to study the prognostic value of GLMS in TCGA-COAD and GSE39582 cohorts. The molecular mechanism of the prognostic factor was investigated via immune cell infiltration estimation and correlation analysis of cancer hallmark pathways. Single-cell transcriptomic dataset GSE146771 was used to identify the cell populations which glycerolipid metabolism targeted on.ResultsThe GLMS was found to be associated with tumor location and consensus molecular types (CMSs) of colon cancer in TCGA-COAD cohort (P < 0.05). Patients in the low-GLMS group exhibited poorer overall survival (OS) in TCGA cohort (P = 0.03; HR, 0.63; 95% CI, 0.42–0.94), which was further validated in the GSE39582 dataset (P < 0.001; HR, 0.57; 95% CI, 0.43–0.76). The association between the GLMS and OS remained significant in the multivariable analysis (TCGA cohort: P = 0.04; HR, 0.64; 95% CI, 0.42–0.98; GSE39582 cohort: P < 0.001; HR, 0.60; 95% CI, 0.45–0.80). The GLMS was positively correlated with cancer hallmark pathways including bile acid metabolism, xenobiotic metabolism, and peroxisome and negatively correlated with pathways such as interferon gamma response, allograft rejection, apoptosis, and inflammatory response (P < 0.05). Increased immune infiltration and upregulated expression of immune checkpoints were observed in patients with lower GLMS (P < 0.05). Single-cell datasets verified the different distribution of GLMS in cell subsets, with significant enrichment of GLMS in malignant cells and Tprolif cells.ConclusionWe demonstrated that GLMS was a potential independent prognostic factor for colon cancer. The GLMS was also correlated with several cancer hallmark pathways, as well as immune microenvironment.https://www.frontiersin.org/articles/10.3389/fonc.2022.881953/fullglycerolipid metabolismcolon cancerprognostic signatureoverall survivalmulti-omics characterization |
| spellingShingle | Zhiyu Wang Zhuoqi Zhang Ke Zhang Qiaoxia Zhou Sidong Chen Hao Zheng Guoqiang Wang Shangli Cai Fujing Wang Shenglong Li Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer Frontiers in Oncology glycerolipid metabolism colon cancer prognostic signature overall survival multi-omics characterization |
| title | Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer |
| title_full | Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer |
| title_fullStr | Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer |
| title_full_unstemmed | Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer |
| title_short | Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer |
| title_sort | multi omics characterization of a glycerolipid metabolism related gene enrichment score in colon cancer |
| topic | glycerolipid metabolism colon cancer prognostic signature overall survival multi-omics characterization |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.881953/full |
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