An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma
Background: Tumor mutational burden (TMB) was verified to be closely associated with immune checkpoint inhibitors, but it is unclear whether gene mutation has an effect on immunotherapy of hepatocellular carcinoma (HCC). This research aimed to investigate the underlying correlation between gene muta...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00853/full |
| _version_ | 1818514789100421120 |
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| author | Zhuomao Mo Yongdan Wang Zhirui Cao Pan Li Shijun Zhang |
| author_facet | Zhuomao Mo Yongdan Wang Zhirui Cao Pan Li Shijun Zhang |
| author_sort | Zhuomao Mo |
| collection | DOAJ |
| description | Background: Tumor mutational burden (TMB) was verified to be closely associated with immune checkpoint inhibitors, but it is unclear whether gene mutation has an effect on immunotherapy of hepatocellular carcinoma (HCC). This research aimed to investigate the underlying correlation between gene mutation and immunotherapy in HCC.Methods: The somatic gene mutation data and gene expression data were retrieved from International Cancer Genome Consortium database and The Cancer Genome Atlas (TCGA) database. The mutational genes were selected by the intersection of three cohorts and further identified using survival analysis and TMB correlation analysis. After the identification of key mutational gene, we explored the correlation between gene mutation and both the immune cell infiltration and immune inhibitors. The signaling pathways associated with gene mutation were confirmed through gene set enrichment analysis. Furthermore, the survival analysis and mutational analysis based on TCGA cohort were performed for the validation of included gene.Results: As one of the frequently mutational genes in HCC, CTNNB1 was finally included in our research, for which it showed the significant result in survival analysis and the positive association with TMB of the three cohorts. Meanwhile, the validation of TCGA showed the significant results. Furthermore, natural killer (NK) cells and neutrophil were found to significantly infiltrate CTNNB1 mutation group from two cohorts. Besides, further analysis demonstrated that four types of immune inhibitors (CD96, HAVCR2, LGALS9, and TGFB1) were downregulated in CTNNB1 mutation group.Conclusion: Our research firstly revealed the underlying association between CTNNB1 mutation and immunotherapy, and we speculated that CTNNB1 mutation may modulate NK cells by affecting CD96. However, more functional experiments should be performed for verification. |
| first_indexed | 2024-12-11T00:20:34Z |
| format | Article |
| id | doaj.art-3e5b53a979c145ba8cacb6c3bfeab258 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T00:20:34Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3e5b53a979c145ba8cacb6c3bfeab2582022-12-22T01:27:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-06-011010.3389/fonc.2020.00853550081An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular CarcinomaZhuomao MoYongdan WangZhirui CaoPan LiShijun ZhangBackground: Tumor mutational burden (TMB) was verified to be closely associated with immune checkpoint inhibitors, but it is unclear whether gene mutation has an effect on immunotherapy of hepatocellular carcinoma (HCC). This research aimed to investigate the underlying correlation between gene mutation and immunotherapy in HCC.Methods: The somatic gene mutation data and gene expression data were retrieved from International Cancer Genome Consortium database and The Cancer Genome Atlas (TCGA) database. The mutational genes were selected by the intersection of three cohorts and further identified using survival analysis and TMB correlation analysis. After the identification of key mutational gene, we explored the correlation between gene mutation and both the immune cell infiltration and immune inhibitors. The signaling pathways associated with gene mutation were confirmed through gene set enrichment analysis. Furthermore, the survival analysis and mutational analysis based on TCGA cohort were performed for the validation of included gene.Results: As one of the frequently mutational genes in HCC, CTNNB1 was finally included in our research, for which it showed the significant result in survival analysis and the positive association with TMB of the three cohorts. Meanwhile, the validation of TCGA showed the significant results. Furthermore, natural killer (NK) cells and neutrophil were found to significantly infiltrate CTNNB1 mutation group from two cohorts. Besides, further analysis demonstrated that four types of immune inhibitors (CD96, HAVCR2, LGALS9, and TGFB1) were downregulated in CTNNB1 mutation group.Conclusion: Our research firstly revealed the underlying association between CTNNB1 mutation and immunotherapy, and we speculated that CTNNB1 mutation may modulate NK cells by affecting CD96. However, more functional experiments should be performed for verification.https://www.frontiersin.org/article/10.3389/fonc.2020.00853/fullhepatocellular carcinomaCTNNB1gene mutationimmunotherapyimmune inhibitor |
| spellingShingle | Zhuomao Mo Yongdan Wang Zhirui Cao Pan Li Shijun Zhang An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma Frontiers in Oncology hepatocellular carcinoma CTNNB1 gene mutation immunotherapy immune inhibitor |
| title | An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma |
| title_full | An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma |
| title_fullStr | An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma |
| title_full_unstemmed | An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma |
| title_short | An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma |
| title_sort | integrative analysis reveals the underlying association between ctnnb1 mutation and immunotherapy in hepatocellular carcinoma |
| topic | hepatocellular carcinoma CTNNB1 gene mutation immunotherapy immune inhibitor |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00853/full |
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