Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a p...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1074123/full |
| _version_ | 1811200689739661312 |
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| author | Zheng Zhou Yusong Zhou Dongbo Liu Qingping Yang Mengjie Tang Wei Liu |
| author_facet | Zheng Zhou Yusong Zhou Dongbo Liu Qingping Yang Mengjie Tang Wei Liu |
| author_sort | Zheng Zhou |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy. |
| first_indexed | 2024-04-12T02:08:09Z |
| format | Article |
| id | doaj.art-ad400bd4c55b45c7aef10a80bf8d9201 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T02:08:09Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ad400bd4c55b45c7aef10a80bf8d92012022-12-22T03:52:29ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-12-011310.3389/fphar.2022.10741231074123Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinomaZheng Zhou0Yusong Zhou1Dongbo Liu2Qingping Yang3Mengjie Tang4Wei Liu5Department of Otolaryngology Head and Neck, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Zunyi Medical University, Zunyi, ChinaDepartment of Pharmacy, Zunyi Medical University, Zunyi, ChinaDepartment of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, ChinaDepartment of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, ChinaHepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy.https://www.frontiersin.org/articles/10.3389/fphar.2022.1074123/fullcuproptosisHCCprognosticimmunemutation landscape |
| spellingShingle | Zheng Zhou Yusong Zhou Dongbo Liu Qingping Yang Mengjie Tang Wei Liu Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma Frontiers in Pharmacology cuproptosis HCC prognostic immune mutation landscape |
| title | Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma |
| title_full | Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma |
| title_fullStr | Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma |
| title_full_unstemmed | Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma |
| title_short | Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma |
| title_sort | prognostic and immune correlation evaluation of a novel cuproptosis related genes signature in hepatocellular carcinoma |
| topic | cuproptosis HCC prognostic immune mutation landscape |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1074123/full |
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