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02 August 2021 : Database Analysis

[In Press] RNA N6-Methyladenosine Patterns in Hepatocellular Carcinoma Reveal a Distinct Immune Infiltration Landscape and Clinical Significance

Hua Zhao1CEFG, Qiujun Zhou2BDEF, Chengwei Shi2CD, Yaojian Shao2CD, Junjie Ni2CD, Jianying Lou3ACE, Shenyu Wei2ACEF

DOI: 10.12659/MSM.930994

Med Sci Monit In Press; DOI: 10.12659/MSM.930994  

Available online: 2021-08-02, In Press, Corrected Proof

Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule


RNA N6-methyladenosine (m6A) methylation, the most abundant and prominent form of epigenetic modification, is involved in hepatocellular carcinoma (HCC) initiation and progression. However, the role of m6A methylation in HCC tumor microenvironment (TME) formation is unexplored. This study aimed to reveal the TME features of HCC patients with distinct m⁶A expression patterns and establish a prognostic model based on m⁶A signatures for HCC cohorts.
We classified the m⁶A methylation patterns in 365 HCC samples based on 21 m6A modulators using a consensus clustering algorithm. Single-sample gene set enrichment analysis algorithm was used to quantify the abundance of immune cell infiltration. Gene set variation analysis revealed the biological characteristics between the m⁶A modification patterns. The m6A-based prognostic model was constructed using a training set with least absolute shrinkage and selection operator regression and validated in internal and external datasets.
Two distinct m⁶A modification patterns exhibiting different TME immune-infiltrating characteristics, heterogeneity, and prognostic variations were identified in the HCC cohort. After depicting the immune landscape of TME in HCC, we found patients with high LRPPRC m⁶A modulator expression had depletion of T cells, cytotoxic cells, dendritic cells, and cytolytic activity response. A high m⁶A score, characterized by suppression of immunity, indicated an immune-excluded TME phenotype, with poor survival. A nomogram was developed to facilitate HCC clinical decision making.
Our results highlight the nonnegligible role of m6A methylation in TME formation and reveal a potential clinical application of the m⁶A-associated prognostic model for patients with HCC.

Keywords: Carcinoma, Hepatocellular; Methylation; Prognosis; Tumor Microenvironment


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Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.934766

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750