Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma
Background: Tumor cells outcompete T cells for methionine via overexpressing SLC43A2, causing T cells exhaustion. We explored the influence of SLC43A2 on tumor immune microenvironment (TIME), immune-related genes (IRGs) and the prognosis of liver hepatocellular carcinoma (LIHC) patients.Methods: The...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.911378/full |
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| author | Yan Liao Yan Liao Junmei Weng Lian Chen Nan Hu Xun Yuan Jianhua Wang Feng He Yixin Cai Qin Huang Jianing Wang Liu Huang |
| author_facet | Yan Liao Yan Liao Junmei Weng Lian Chen Nan Hu Xun Yuan Jianhua Wang Feng He Yixin Cai Qin Huang Jianing Wang Liu Huang |
| author_sort | Yan Liao |
| collection | DOAJ |
| description | Background: Tumor cells outcompete T cells for methionine via overexpressing SLC43A2, causing T cells exhaustion. We explored the influence of SLC43A2 on tumor immune microenvironment (TIME), immune-related genes (IRGs) and the prognosis of liver hepatocellular carcinoma (LIHC) patients.Methods: The TCGA-LIHC dataset (n = 374) and the ICGC-LIRI-JP-LIHC (n = 231) datasets were used as training and validation cohort, respectively. IRGs were obtained from ImmPort. Statistical analyses were performed using R (V 4.0.5). Online databases such as GEPIA, GSCALite, the Kaplan–Meier plotter, KEGG, TIMER2, and CMap were used for differential expression, immune infiltration, functional enrichment, survival, and drug-induced gene perturbation analysis.Results: SLC43A2 expression was higher in LIHC, correlated with worse survival, but could not predict prognosis of LIHC separately (AUC = 0.467). SLC43A2 positively correlated with immune exhaustion markers (all p < 0.001) and with increased infiltration of Tregs, macrophages and myeloid-derived suppressor cells (MDSC) (all p < 0.05). SLC43A2 may regulate 120 IRGs. A prognostic risk score model was developed using the TCGA-LIHC cohort and validated by the ICGC-LIRI-JP cohort. Arachidonic acid, SB-202190 and guanethidine were identified as possible immunomodulators pharmacologically targeting SLC43A2 in LIHC.Conclusion: SLC43A2 may create suppressive tumor microenvironment and regulate related IRGs, thus affecting the prognosis of LIHC. Arachidonic acid, SB-202190, and guanethidine may be worthy of further study as immunomodulators on SLC43A2. |
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| language | English |
| last_indexed | 2024-04-11T09:57:50Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-ed80d1d99dd249bba19b6618c007fa632022-12-22T04:30:32ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.911378911378Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinomaYan Liao0Yan Liao1Junmei Weng2Lian Chen3Nan Hu4Xun Yuan5Jianhua Wang6Feng He7Yixin Cai8Qin Huang9Jianing Wang10Liu Huang11Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaThe Reproductive Medical Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Neurology and Laboratory of Clinical Genetics, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaBackground: Tumor cells outcompete T cells for methionine via overexpressing SLC43A2, causing T cells exhaustion. We explored the influence of SLC43A2 on tumor immune microenvironment (TIME), immune-related genes (IRGs) and the prognosis of liver hepatocellular carcinoma (LIHC) patients.Methods: The TCGA-LIHC dataset (n = 374) and the ICGC-LIRI-JP-LIHC (n = 231) datasets were used as training and validation cohort, respectively. IRGs were obtained from ImmPort. Statistical analyses were performed using R (V 4.0.5). Online databases such as GEPIA, GSCALite, the Kaplan–Meier plotter, KEGG, TIMER2, and CMap were used for differential expression, immune infiltration, functional enrichment, survival, and drug-induced gene perturbation analysis.Results: SLC43A2 expression was higher in LIHC, correlated with worse survival, but could not predict prognosis of LIHC separately (AUC = 0.467). SLC43A2 positively correlated with immune exhaustion markers (all p < 0.001) and with increased infiltration of Tregs, macrophages and myeloid-derived suppressor cells (MDSC) (all p < 0.05). SLC43A2 may regulate 120 IRGs. A prognostic risk score model was developed using the TCGA-LIHC cohort and validated by the ICGC-LIRI-JP cohort. Arachidonic acid, SB-202190 and guanethidine were identified as possible immunomodulators pharmacologically targeting SLC43A2 in LIHC.Conclusion: SLC43A2 may create suppressive tumor microenvironment and regulate related IRGs, thus affecting the prognosis of LIHC. Arachidonic acid, SB-202190, and guanethidine may be worthy of further study as immunomodulators on SLC43A2.https://www.frontiersin.org/articles/10.3389/fgene.2022.911378/fullliver hepatocellular carcinoma (LIHC)SLC43A2tumor immune microenvironment (TIME)prognostic risk score modelprognostic biomarkertherapeutic target |
| spellingShingle | Yan Liao Yan Liao Junmei Weng Lian Chen Nan Hu Xun Yuan Jianhua Wang Feng He Yixin Cai Qin Huang Jianing Wang Liu Huang Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma Frontiers in Genetics liver hepatocellular carcinoma (LIHC) SLC43A2 tumor immune microenvironment (TIME) prognostic risk score model prognostic biomarker therapeutic target |
| title | Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma |
| title_full | Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma |
| title_fullStr | Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma |
| title_full_unstemmed | Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma |
| title_short | Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma |
| title_sort | comprehensive analysis of slc43a2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma |
| topic | liver hepatocellular carcinoma (LIHC) SLC43A2 tumor immune microenvironment (TIME) prognostic risk score model prognostic biomarker therapeutic target |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.911378/full |
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