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

التفاصيل البيبلوغرافية
العنوان: Identification and Characterization of Alcohol-related Hepatocellular Carcinoma Prognostic Subtypes based on an Integrative N6-methyladenosine methylation Model.
المؤلفون: Zhang Y; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Zeng F; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Zeng M; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Han X; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Cai L; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Zhang J; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Weng J; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Gao Y; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.
المصدر: International journal of biological sciences [Int J Biol Sci] 2021 Aug 14; Vol. 17 (13), pp. 3554-3572. Date of Electronic Publication: 2021 Aug 14 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Ivyspring International Country of Publication: Australia NLM ID: 101235568 Publication Model: eCollection Cited Medium: Internet ISSN: 1449-2288 (Electronic) Linking ISSN: 14492288 NLM ISO Abbreviation: Int J Biol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Lake Haven, N.S.W., Australia : Ivyspring International, c2004-
مواضيع طبية MeSH: Gene Expression Regulation, Neoplastic* , Nomograms*, Adenosine/*analogs & derivatives , Carcinoma, Hepatocellular/*metabolism , Liver Neoplasms/*metabolism, Adenosine/metabolism ; Alcohol Drinking/adverse effects ; Animals ; Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/etiology ; Case-Control Studies ; DNA Methylation ; Drug Screening Assays, Antitumor ; Humans ; Liver Neoplasms/diagnosis ; Liver Neoplasms/drug therapy ; Liver Neoplasms/etiology ; Mice, Inbred C57BL ; Teniposide/therapeutic use ; Mice
مستخلص: 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.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
التعليقات: Erratum in: Int J Biol Sci. 2022 Nov 3;18(16):6227-6228. (PMID: 36439871)
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فهرسة مساهمة: Keywords: Hepatocellular carcinoma; N6-methyladenosine; teniposide; treatment sensitivity; tumour immune microenvironment
المشرفين على المادة: 0 (Antineoplastic Agents)
957E6438QA (Teniposide)
CLE6G00625 (N-methyladenosine)
K72T3FS567 (Adenosine)
تواريخ الأحداث: Date Created: 20210913 Date Completed: 20220222 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC8416726
DOI: 10.7150/ijbs.62168
PMID: 34512165
قاعدة البيانات: MEDLINE
الوصف
تدمد:1449-2288
DOI:10.7150/ijbs.62168