期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 17, 期 13, 页码 3554-3572出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.62168
关键词
Hepatocellular carcinoma; N6-methyladenosine; tumour immune microenvironment; treatment sensitivity; teniposide
资金
- China Postdoctoral Science Foundation [F121ZJ0216, 2021M691463]
- National Key R&D Program of China [2018YFC1106400, 2018YFA0108200]
- Science and Technology Planning Project of Guangdong Province [2015B020229002]
- National Natural Science Foundation of China [31972926]
- Natural Science Foundation of Guangdong Province [2014A030312013, 2018A030313128]
- Guangdong key research and development plan [2019B020234003]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515111111]
The study constructed an integrative m6A model based on A-HCC subtyping and mechanism exploration, identifying high/low-risk subtypes of A-HCC patients. The high-risk subtype showed poor prognosis, immunosuppression, and activation of pathways related to tumorigenesis and proliferation.
Background: Alcohol consumption increases the risk of hepatocellular carcinoma (HCC), and associated with a high mortality rate and poor prognosis. N6-methyladenosine (m6A) methylations play key roles in tumorigenesis and progression. However, our current knowledge about m6A in alcohol-related HCC (A-HCC) remains elucidated. Herein, the authors construct an integrative m6A model based on A-HCC subtyping and mechanism exploration workflow. Methods: Based on the m6A expressions of A-HCC and in vivo experiment, different prognosis risk A-HCC subtypes are identified. Meanwhile, multiple interdependent indicators of prognosis including patient survival rate, clinical pathological prognosis and immunotherapy sensitivity. Results: The m6A model includes LRPPRC, YTHDF2, KIAA14219, and RBM15B, classified A-HCC patients into high/low-risk subtypes. The high-risk subtype compared to the low-risk subtype showed phenotypic malignancy, poor prognosis, immunosuppression, and activation of tumorigenesis and proliferation-related pathways, including the E2F target, DNA repair, and mTORC1 signalling pathways. The expression of Immunosuppressive cytokines DNMT1/EZH2 was up-regulated in A-HCC patients, and teniposide may be a potential therapeutic drug for A-HCC. Conclusion: Our model redefined A-HCC prognosis risk, identified potential m6As linking tumour progress and immune regulations and selected possible therapy target, thus promoting understanding and clinical applications about A-HCC.
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