Frontiers in Immunology (Sep 2022)
Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma
- 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
Affiliations
- Ping Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Ping Liu
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Ziqing Zhu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Ziqing Zhu
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Jiayao Ma
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Jiayao Ma
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Le Wei
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Le Wei
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Ying Han
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Ying Han
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Edward Shen
- Department of Life Science, McMaster University, Hamilton, ON, Canada
- Xiao Tan
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yihong Chen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yihong Chen
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Changjing Cai
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Changjing Cai
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Cao Guo
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Cao Guo
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Yinghui Peng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yinghui Peng
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Yan Gao
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yan Gao
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Yongting Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yongting Liu
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Qiaoqiao Huang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Qiaoqiao Huang
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Le Gao
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Le Gao
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Yin Li
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yin Li
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Zhaohui Jiang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Zhaohui Jiang
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Wantao Wu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Wantao Wu
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Yihan Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Yihan Liu
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Shan Zeng
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Shan Zeng
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Wei Li
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Wei Li
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Ziyang Feng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Ziyang Feng
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Hong Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- Hong Shen
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
- Hong Shen
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- DOI
- https://doi.org/10.3389/fimmu.2022.951529
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
