RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis
Abstract Background Methylation at the N 6 atom of adenosine (m6A) of RNA has been linked to immune responses to various types of tumors. How m6A methylation affects tumorigenicity, progression, and tumor microenvironment in hepatocellular carcinoma (HCC) is unclear. Methods Consensus clustering was...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02965-7 |
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| author | Zongcai Yan Meiling He Lifeng He Liuxia Wei Yumei Zhang |
| author_facet | Zongcai Yan Meiling He Lifeng He Liuxia Wei Yumei Zhang |
| author_sort | Zongcai Yan |
| collection | DOAJ |
| description | Abstract Background Methylation at the N 6 atom of adenosine (m6A) of RNA has been linked to immune responses to various types of tumors. How m6A methylation affects tumorigenicity, progression, and tumor microenvironment in hepatocellular carcinoma (HCC) is unclear. Methods Consensus clustering was used to define m6A methylation patterns based on expression of 26 regulatory factors in HCC. The relative abundance of various immune cell types in the tumor microenvironment was quantified using single-sample gene set enrichment analysis. Cox regression with LASSO was used to screen for genes whose expression correlated with survival of patients with HCC. Results Two patterns of m6A methylation in HCC were identified: pattern C1 was associated with abundant tumor infiltration by activated CD8+ T cells and by effector memory CD8+ T cells, as well as longer survival; pattern C2 was associated with abundant tumor infiltration by activated CD4+ T cells and by type 2 helper T cells, as well as with shorter survival. Cox regression identified a seven-gene signature capable of predicting the characteristics of the tumor microenvironment and overall survival in HCC: patients in the high-risk group had a lower immunophenoscore, higher TIDE score, and worse survival. Conclusions Patterns of m6A methylation in HCC are related to immune cell characteristics of the tumor microenvironment and to disease progression and prognosis. Analyzing these patterns in detail may clarify when and how the HCC responds to checkpoint inhibitors and guide the personalization of immunotherapy. |
| format | Article |
| id | doaj-art-a703b21ae8a444a7a0d558249e1a3e9d |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-a703b21ae8a444a7a0d558249e1a3e9d2025-08-20T02:06:31ZengSpringerDiscover Oncology2730-60112025-06-0116112010.1007/s12672-025-02965-7RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosisZongcai Yan0Meiling He1Lifeng He2Liuxia Wei3Yumei Zhang4Department of Medical Oncology, Guangxi Medical University Cancer HospitalDepartment of Medical Oncology, Guangxi Medical University Cancer HospitalDepartment of Thoracic Surgery, The People’s Hospital of Guangxi Zhuang Autonomous RegionDepartment of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineDepartment of Medical Oncology, Guangxi Medical University Cancer HospitalAbstract Background Methylation at the N 6 atom of adenosine (m6A) of RNA has been linked to immune responses to various types of tumors. How m6A methylation affects tumorigenicity, progression, and tumor microenvironment in hepatocellular carcinoma (HCC) is unclear. Methods Consensus clustering was used to define m6A methylation patterns based on expression of 26 regulatory factors in HCC. The relative abundance of various immune cell types in the tumor microenvironment was quantified using single-sample gene set enrichment analysis. Cox regression with LASSO was used to screen for genes whose expression correlated with survival of patients with HCC. Results Two patterns of m6A methylation in HCC were identified: pattern C1 was associated with abundant tumor infiltration by activated CD8+ T cells and by effector memory CD8+ T cells, as well as longer survival; pattern C2 was associated with abundant tumor infiltration by activated CD4+ T cells and by type 2 helper T cells, as well as with shorter survival. Cox regression identified a seven-gene signature capable of predicting the characteristics of the tumor microenvironment and overall survival in HCC: patients in the high-risk group had a lower immunophenoscore, higher TIDE score, and worse survival. Conclusions Patterns of m6A methylation in HCC are related to immune cell characteristics of the tumor microenvironment and to disease progression and prognosis. Analyzing these patterns in detail may clarify when and how the HCC responds to checkpoint inhibitors and guide the personalization of immunotherapy.https://doi.org/10.1007/s12672-025-02965-7Hepatocellular carcinomam6A modificationTumor microenvironmentPrognosisImmunotherapy |
| spellingShingle | Zongcai Yan Meiling He Lifeng He Liuxia Wei Yumei Zhang RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis Discover Oncology Hepatocellular carcinoma m6A modification Tumor microenvironment Prognosis Immunotherapy |
| title | RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis |
| title_full | RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis |
| title_fullStr | RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis |
| title_full_unstemmed | RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis |
| title_short | RNA m6A methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis |
| title_sort | rna m6a methylation patterns in hepatocellular carcinoma and their association with characteristics of the tumor microenvironment and prognosis |
| topic | Hepatocellular carcinoma m6A modification Tumor microenvironment Prognosis Immunotherapy |
| url | https://doi.org/10.1007/s12672-025-02965-7 |
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