Identification and Characterization of Alcohol-related Hepatocellular Carcinoma Prognostic Subtypes based on an Integrative N6-methyladenosine methylation Model.

Abstract

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.

• Authors: Yue Zhang, Fanhong Zeng, Min Zeng, Xu Han, Lei Cai, Jiajun Zhang, Jun Weng, Yi Gao
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 17 Issue 13 Pg. 3554-3572 ( 2021) ISSN: 1449-2288 [Electronic] Australia
• PMID: 34512165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Antineoplastic Agents
• Teniposide
• N-methyladenosine
• Adenosine

Topics

• Adenosine (analogs & derivatives, metabolism)
• Alcohol Drinking (adverse effects)
• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (diagnosis, drug therapy, etiology, metabolism)
• Case-Control Studies
• DNA Methylation
• Drug Screening Assays, Antitumor
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (diagnosis, drug therapy, etiology, metabolism)
• Mice, Inbred C57BL
• Nomograms
• Teniposide (therapeutic use)