Construction and validation of an N6‑methyladenosine‑associated prognostic signature in hepatocellular carcinoma

Zhu,Peng; Ren,Qianqian; He,Nan; Zhou,Cheng; Jin,Qianna; Gong,Zhao

doi:10.3892/ol.2021.12482

Construction and validation of an N6‑methyladenosine‑associated prognostic signature in hepatocellular carcinoma

Authors:
- Peng Zhu
- Qianqian Ren
- Nan He
- Cheng Zhou
- Qianna Jin
- Zhao Gong
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Affiliations: Department of Hepatobiliary Surgery, Wuhan No. 1 Hospital, Wuhan, Hubei 430022, P.R. China, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Cancer Center, Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: January 21, 2021 https://doi.org/10.3892/ol.2021.12482
Article Number: 221
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is among the most common types of cancer that threat the public health worldwide. N6‑methyladenosine (m6A) RNA methylation is associated with cancer initiation and progression, and is dynamically regulated by m6A RNA methylation‑associated genes. However, little is known about the expression status and the prognostic value of m6A‑associated genes in HCC. The present study aimed to identify the expression profiling pattern and clinical significance of m6A‑associated genes in HCC. Consensus clustering analysis was performed to identify the clusters of HCC with different clinical outcomes. A prognostic signature built by the least absolute shrinkage and selection operator Cox regression model was utilized to discover subtypes associated with different clinical outcomes of patients with HCC in the discovery cohort from The Cancer Genome Atlas. The differences between subgroups were characterized in terms of epigenetic dysregulation and somatic mutation frequencies. The International Cancer Genome Consortium cohort and two independent cohorts from the meta‑Gene Expression Omnibus database were used for external validation. Most of the m6A‑associated genes were upregulated and involved in the prognosis and malignancy of HCC. A four‑gene prognostic signature revealed two HCC subtypes (namely, high‑ and low‑risk group) that was associated with different clinical outcomes. Patients in the high‑risk group were accompanied with increased epigenetic silencing and significant mutations in TP53 and FLG, while ALB was frequently mutated in the low‑risk group. In conclusion, an m6A‑based signature was constructed to predict the prognosis of patients with HCC, which may provide a tool for reliable prognosis assessment for clinicians, and aid clinical treatment decision‑making.

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