Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis
Cuproptosis represents a novel copper-dependent regulated cell death, distinct from other known cell death processes. In this report, a comprehensive analysis of cuproptosis in hepatocellular carcinoma (HCC) was conducted using multi-omics including genomics, bulk RNA-seq, single cell RNA-seq and pr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1009036/full |
| _version_ | 1811326722988048384 |
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| author | Xinqiang Li Xinqiang Li Peng Jiang Peng Jiang Ruixia Li Bin Wu Bin Wu Kai Zhao Kai Zhao Shipeng Li Jinzhen Cai Jinzhen Cai |
| author_facet | Xinqiang Li Xinqiang Li Peng Jiang Peng Jiang Ruixia Li Bin Wu Bin Wu Kai Zhao Kai Zhao Shipeng Li Jinzhen Cai Jinzhen Cai |
| author_sort | Xinqiang Li |
| collection | DOAJ |
| description | Cuproptosis represents a novel copper-dependent regulated cell death, distinct from other known cell death processes. In this report, a comprehensive analysis of cuproptosis in hepatocellular carcinoma (HCC) was conducted using multi-omics including genomics, bulk RNA-seq, single cell RNA-seq and proteomics. ATP7A, PDHA1 and DLST comprised the top 3 mutation genes in The Cancer Genome Atlas (TCGA)-LIHC; 9 cuproptosis-related genes showed significant, independent prognostic values. Cuproptosis-related hepatocytes were identified and their function were evaluated in single cell assays. Based on cuproptosis-related gene expressions, two immune patterns were found, with the cuproptosis-C1 subtype identified as a cytotoxic immune pattern, while the cuproptosis-C2 subtype was identified as a regulatory immune pattern. Cuproptosis-C2 was associated with a number of pathways involving tumorigenesis. A prognosis model based on differentially expressed genes (DEGs) of cuproptosis patterns was constructed and validated. We established a cuproptosis index (CPI) and further performed an analysis of its clinical relevance. High CPI values were associated with increased levels of alpha-fetoprotein (AFP) and advanced tumor stages. Taken together, this comprehensive analysis provides important, new insights into cuproptosis mechanisms associated with human HCC. |
| first_indexed | 2024-04-13T14:54:38Z |
| format | Article |
| id | doaj.art-c10c65c809014968913b154d68293f14 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T14:54:38Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c10c65c809014968913b154d68293f142022-12-22T02:42:29ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10090361009036Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosisXinqiang Li0Xinqiang Li1Peng Jiang2Peng Jiang3Ruixia Li4Bin Wu5Bin Wu6Kai Zhao7Kai Zhao8Shipeng Li9Jinzhen Cai10Jinzhen Cai11Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, ChinaOrgan Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, ChinaOrgan Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, ChinaOrgan Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, ChinaThe Second Clinical Medical College, Capital Medical University, Beijing, ChinaOrgan Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, ChinaCuproptosis represents a novel copper-dependent regulated cell death, distinct from other known cell death processes. In this report, a comprehensive analysis of cuproptosis in hepatocellular carcinoma (HCC) was conducted using multi-omics including genomics, bulk RNA-seq, single cell RNA-seq and proteomics. ATP7A, PDHA1 and DLST comprised the top 3 mutation genes in The Cancer Genome Atlas (TCGA)-LIHC; 9 cuproptosis-related genes showed significant, independent prognostic values. Cuproptosis-related hepatocytes were identified and their function were evaluated in single cell assays. Based on cuproptosis-related gene expressions, two immune patterns were found, with the cuproptosis-C1 subtype identified as a cytotoxic immune pattern, while the cuproptosis-C2 subtype was identified as a regulatory immune pattern. Cuproptosis-C2 was associated with a number of pathways involving tumorigenesis. A prognosis model based on differentially expressed genes (DEGs) of cuproptosis patterns was constructed and validated. We established a cuproptosis index (CPI) and further performed an analysis of its clinical relevance. High CPI values were associated with increased levels of alpha-fetoprotein (AFP) and advanced tumor stages. Taken together, this comprehensive analysis provides important, new insights into cuproptosis mechanisms associated with human HCC.https://www.frontiersin.org/articles/10.3389/fonc.2022.1009036/fullcuproptosiscell deathomicsHCCsingle cell RNA analysis |
| spellingShingle | Xinqiang Li Xinqiang Li Peng Jiang Peng Jiang Ruixia Li Bin Wu Bin Wu Kai Zhao Kai Zhao Shipeng Li Jinzhen Cai Jinzhen Cai Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis Frontiers in Oncology cuproptosis cell death omics HCC single cell RNA analysis |
| title | Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis |
| title_full | Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis |
| title_fullStr | Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis |
| title_full_unstemmed | Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis |
| title_short | Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis |
| title_sort | analysis of cuproptosis in hepatocellular carcinoma using multi omics reveals a comprehensive hcc landscape and the immune patterns of cuproptosis |
| topic | cuproptosis cell death omics HCC single cell RNA analysis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1009036/full |
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