Risk model of hepatocellular carcinoma based on cuproptosis-related genes
Background: Owing to the heterogeneity displayed by hepatocellular carcinoma (HCC) and the complexity of tumor microenvironment (TME), it is noted that the long-term effectiveness of the cancer therapy poses a severe clinical challenge. Hence, it is essential to categorize and alter the treatment in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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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.2022.1000652/full |
| _version_ | 1811267857567186944 |
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| author | Zhiqiang Liu Yong Qi Haibo Wang Qikun Zhang Zhengsheng Wu Wenyong Wu |
| author_facet | Zhiqiang Liu Yong Qi Haibo Wang Qikun Zhang Zhengsheng Wu Wenyong Wu |
| author_sort | Zhiqiang Liu |
| collection | DOAJ |
| description | Background: Owing to the heterogeneity displayed by hepatocellular carcinoma (HCC) and the complexity of tumor microenvironment (TME), it is noted that the long-term effectiveness of the cancer therapy poses a severe clinical challenge. Hence, it is essential to categorize and alter the treatment intervention decisions for these tumors.Materials and methods: “ConsensusClusterPlus” tool was used for developing a secure molecular classification system that was based on the cuproptosis-linked gene expression. Furthermore, all clinical properties, pathway characteristics, genomic changes, and immune characteristics of different cell types involved in the immune pathways were also assessed. Univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) analyses were used for designing the prognostic risk model associated with cuproptosis.Results: Three cuproptosis-linked subtypes (clust1, clust2, and clust3) were detected. Out of these, Clust3 showed the worst prognosis, followed by clust2, while Clust1 showed the best prognosis. Three subtypes had significantly different enrichment in pathways related to Tricarboxylic Acid (TCA) cycle, cell cycle, and cell senescence (p < 0.01). The clust3 subtype with poor prognosis had a low “ImmuneScore” and low immune cell infiltration, and the three subtypes had significant differences in the antigen processing and presentation pathway of the macrophages. Clust1 had a low TIDE score and was sensitive to immunotherapy. Then, according to the prognosis-related genes of cuproptosis, a prognosis risk model related to cuproptosis was constructed, containing seven genes (KIF2C, PTTG1, CENPM, CDC20, CYP2C9, SFN, and CFHR3). “High” group had a higher TIDE score compared to the TIDE score value shown by the “Low” group, which benefited less from immunotherapy, whereas the “High” group patients were more sensitive to the conventional drugs. Finally, the prognosis risk model related to cuproptosis was combined with clinical pathological characteristics to further improve the prognostic model and survival prediction.Conclusion: Three new molecular subgroups based on cuproptosis-linked genes were revealed, and a cuproptosis-related prognostic risk model comprising seven genes was established in this study, which could assist in predicting the prognosis and identifying the patients benefit from immunotherapy. |
| first_indexed | 2024-04-12T21:10:13Z |
| format | Article |
| id | doaj.art-234346e6f2134fabac2093993ea46449 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T21:10:13Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-234346e6f2134fabac2093993ea464492022-12-22T03:16:36ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.10006521000652Risk model of hepatocellular carcinoma based on cuproptosis-related genesZhiqiang Liu0Yong Qi1Haibo Wang2Qikun Zhang3Zhengsheng Wu4Wenyong Wu5Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaBackground: Owing to the heterogeneity displayed by hepatocellular carcinoma (HCC) and the complexity of tumor microenvironment (TME), it is noted that the long-term effectiveness of the cancer therapy poses a severe clinical challenge. Hence, it is essential to categorize and alter the treatment intervention decisions for these tumors.Materials and methods: “ConsensusClusterPlus” tool was used for developing a secure molecular classification system that was based on the cuproptosis-linked gene expression. Furthermore, all clinical properties, pathway characteristics, genomic changes, and immune characteristics of different cell types involved in the immune pathways were also assessed. Univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) analyses were used for designing the prognostic risk model associated with cuproptosis.Results: Three cuproptosis-linked subtypes (clust1, clust2, and clust3) were detected. Out of these, Clust3 showed the worst prognosis, followed by clust2, while Clust1 showed the best prognosis. Three subtypes had significantly different enrichment in pathways related to Tricarboxylic Acid (TCA) cycle, cell cycle, and cell senescence (p < 0.01). The clust3 subtype with poor prognosis had a low “ImmuneScore” and low immune cell infiltration, and the three subtypes had significant differences in the antigen processing and presentation pathway of the macrophages. Clust1 had a low TIDE score and was sensitive to immunotherapy. Then, according to the prognosis-related genes of cuproptosis, a prognosis risk model related to cuproptosis was constructed, containing seven genes (KIF2C, PTTG1, CENPM, CDC20, CYP2C9, SFN, and CFHR3). “High” group had a higher TIDE score compared to the TIDE score value shown by the “Low” group, which benefited less from immunotherapy, whereas the “High” group patients were more sensitive to the conventional drugs. Finally, the prognosis risk model related to cuproptosis was combined with clinical pathological characteristics to further improve the prognostic model and survival prediction.Conclusion: Three new molecular subgroups based on cuproptosis-linked genes were revealed, and a cuproptosis-related prognostic risk model comprising seven genes was established in this study, which could assist in predicting the prognosis and identifying the patients benefit from immunotherapy.https://www.frontiersin.org/articles/10.3389/fgene.2022.1000652/fullliver cancercuproptosismolecular subtyperisk scoreprognosistumor immunity |
| spellingShingle | Zhiqiang Liu Yong Qi Haibo Wang Qikun Zhang Zhengsheng Wu Wenyong Wu Risk model of hepatocellular carcinoma based on cuproptosis-related genes Frontiers in Genetics liver cancer cuproptosis molecular subtype risk score prognosis tumor immunity |
| title | Risk model of hepatocellular carcinoma based on cuproptosis-related genes |
| title_full | Risk model of hepatocellular carcinoma based on cuproptosis-related genes |
| title_fullStr | Risk model of hepatocellular carcinoma based on cuproptosis-related genes |
| title_full_unstemmed | Risk model of hepatocellular carcinoma based on cuproptosis-related genes |
| title_short | Risk model of hepatocellular carcinoma based on cuproptosis-related genes |
| title_sort | risk model of hepatocellular carcinoma based on cuproptosis related genes |
| topic | liver cancer cuproptosis molecular subtype risk score prognosis tumor immunity |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1000652/full |
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