Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma
BackgroundImmunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.951529/full |
| _version_ | 1818480009017294848 |
|---|---|
| author | Ping Liu Ping Liu Ziqing Zhu Ziqing Zhu Jiayao Ma Jiayao Ma Le Wei Le Wei Ying Han Ying Han Edward Shen Xiao Tan Yihong Chen Yihong Chen Changjing Cai Changjing Cai Cao Guo Cao Guo Yinghui Peng Yinghui Peng Yan Gao Yan Gao Yongting Liu Yongting Liu Qiaoqiao Huang Qiaoqiao Huang Le Gao Le Gao Yin Li Yin Li Zhaohui Jiang Zhaohui Jiang Wantao Wu Wantao Wu Yihan Liu Yihan Liu Shan Zeng Shan Zeng Shan Zeng Wei Li Wei Li Ziyang Feng Ziyang Feng Hong Shen Hong Shen Hong Shen |
| author_facet | Ping Liu Ping Liu Ziqing Zhu Ziqing Zhu Jiayao Ma Jiayao Ma Le Wei Le Wei Ying Han Ying Han Edward Shen Xiao Tan Yihong Chen Yihong Chen Changjing Cai Changjing Cai Cao Guo Cao Guo Yinghui Peng Yinghui Peng Yan Gao Yan Gao Yongting Liu Yongting Liu Qiaoqiao Huang Qiaoqiao Huang Le Gao Le Gao Yin Li Yin Li Zhaohui Jiang Zhaohui Jiang Wantao Wu Wantao Wu Yihan Liu Yihan Liu Shan Zeng Shan Zeng Shan Zeng Wei Li Wei Li Ziyang Feng Ziyang Feng Hong Shen Hong Shen Hong Shen |
| author_sort | Ping Liu |
| collection | DOAJ |
| description | BackgroundImmunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified.MethodsIn this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models.ResultsThe 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis.ConclusionIn conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis. |
| first_indexed | 2024-12-10T11:17:24Z |
| format | Article |
| id | doaj.art-72b98fb785184749afd48020c79bcf70 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T11:17:24Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-72b98fb785184749afd48020c79bcf702022-12-22T01:51:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.951529951529Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinomaPing Liu0Ping Liu1Ziqing Zhu2Ziqing Zhu3Jiayao Ma4Jiayao Ma5Le Wei6Le Wei7Ying Han8Ying Han9Edward Shen10Xiao Tan11Yihong Chen12Yihong Chen13Changjing Cai14Changjing Cai15Cao Guo16Cao Guo17Yinghui Peng18Yinghui Peng19Yan Gao20Yan Gao21Yongting Liu22Yongting Liu23Qiaoqiao Huang24Qiaoqiao Huang25Le Gao26Le Gao27Yin Li28Yin Li29Zhaohui Jiang30Zhaohui Jiang31Wantao Wu32Wantao Wu33Yihan Liu34Yihan Liu35Shan Zeng36Shan Zeng37Shan Zeng38Wei Li39Wei Li40Ziyang Feng41Ziyang Feng42Hong Shen43Hong Shen44Hong Shen45Department of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Life Science, McMaster University, Hamilton, ON, CanadaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaBackgroundImmunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified.MethodsIn this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models.ResultsThe 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis.ConclusionIn conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.951529/fullm5Cimmunotherapybiomarkerdrug sensitivityHCCprecision medicine |
| spellingShingle | Ping Liu Ping Liu Ziqing Zhu Ziqing Zhu Jiayao Ma Jiayao Ma Le Wei Le Wei Ying Han Ying Han Edward Shen Xiao Tan Yihong Chen Yihong Chen Changjing Cai Changjing Cai Cao Guo Cao Guo Yinghui Peng Yinghui Peng Yan Gao Yan Gao Yongting Liu Yongting Liu Qiaoqiao Huang Qiaoqiao Huang Le Gao Le Gao Yin Li Yin Li Zhaohui Jiang Zhaohui Jiang Wantao Wu Wantao Wu Yihan Liu Yihan Liu Shan Zeng Shan Zeng Shan Zeng Wei Li Wei Li Ziyang Feng Ziyang Feng Hong Shen Hong Shen Hong Shen Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma Frontiers in Immunology m5C immunotherapy biomarker drug sensitivity HCC precision medicine |
| title | Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma |
| title_full | Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma |
| title_fullStr | Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma |
| title_full_unstemmed | Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma |
| title_short | Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma |
| title_sort | prognostic stratification based on m5c regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma |
| topic | m5C immunotherapy biomarker drug sensitivity HCC precision medicine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.951529/full |
| work_keys_str_mv | AT pingliu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT pingliu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT ziqingzhu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT ziqingzhu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT jiayaoma prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT jiayaoma prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT lewei prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT lewei prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yinghan prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yinghan prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT edwardshen prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT xiaotan prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yihongchen prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yihongchen prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT changjingcai prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT changjingcai prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT caoguo prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT caoguo prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yinghuipeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yinghuipeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yangao prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yangao prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yongtingliu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yongtingliu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT qiaoqiaohuang prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT qiaoqiaohuang prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT legao prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT legao prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yinli prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yinli prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT zhaohuijiang prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT zhaohuijiang prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT wantaowu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT wantaowu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yihanliu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT yihanliu prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT shanzeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT shanzeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT shanzeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT weili prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT weili prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT ziyangfeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT ziyangfeng prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT hongshen prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT hongshen prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma AT hongshen prognosticstratificationbasedonm5cregulatorsactsasanovelbiomarkerforimmunotherapyinhepatocellularcarcinoma |