Journal of Hepatocellular Carcinoma (Mar 2021)
Gene Expression Profile and Prognostic Value of m6A RNA Methylation Regulators in Hepatocellular Carcinoma
Abstract
Xian Chang,1,* Yang-Fan Lv,2,* Jing He,3,* Ya Cao,2 Chang-Qing Li,1 Qiao-Nan Guo2 1Department of Orthopedics, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, People’s Republic of China; 2Department of Pathology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, People’s Republic of China; 3Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiao-Nan Guo; Chang-Qing Li Email [email protected]; [email protected]: N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of mammalian RNA, and it is associated with tumorigenesis and cancer progression. Its regulation is mediated via m6A-related regulators, including “erasers,” “readers,” and “writers”. The present study evaluated the expression profile, risk signature and prognostic value of 13 m6A regulators in hepatocellular carcinoma (HCC) using different datasets, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and clinical samples.Methods: We used 374 HCC samples derived from the TCGA database, 569 HCC samples from 2 GEO datasets, and clinical tumour and nontumour tissues derived from 60 patients with HCC who underwent surgery in Xinqiao Hospital Chongqing to assess the gene expression profiles and prognostic values of m6A-related regulators in HCC.Results: Eight of 13 core m6A-related regulators were overexpressed in all databases, including TCGA, GSE, clinical tumour and nontumour tissues of HCC. Two clusters (Cluster 1 and Cluster 2) were identified via consensus clustering. Cluster 2 was associated with poorer prognosis, higher tumour grade, higher AFP levels, and worse outcome compared to Cluster 1, which indicates that these m6A-related regulators are highly correlated with HCC malignancy. We performed survival analyses using the Log rank tests and a Cox regression model. Gene enrichment analysis was used to detect the related KEGG and GO pathways. We derived a prognostic risk signature using five selected m6A-related regulators.Conclusion: Our work suggested that m6A-related regulators might be key participants in the tumour progression of HCC and potential biomarkers with prognostic value.Keywords: RNA modification, N6-methyladenosine, m6A, hepatocellular carcinoma, prognosis, RNA methylation regulators
