Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma

Tianxing Dai; Jing Li; Linsen Ye; Haoyuan Yu; Mingbin Deng; Wei Liu; Hua Li; Yang Yang; Guoying Wang

doi:10.14218/JCTH.2021.00096

Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma

J Clin Transl Hepatol. 2022 Apr 28;10(2):308-320. doi: 10.14218/JCTH.2021.00096. Epub 2021 Jul 13.

Authors

Tianxing Dai¹, Jing Li², Linsen Ye¹, Haoyuan Yu¹, Mingbin Deng¹, Wei Liu³, Hua Li¹, Yang Yang¹, Guoying Wang¹

Affiliations

¹ Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
² Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
³ Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Abstract

Background and aims: Numerous studies have explored the important role of N6-methyladenosine (m⁶A) in cancer. Nonetheless, the interaction between m⁶A and long noncoding RNAs (lncRNAs) is poorly investigated. Herein, we systematically analyzed the role and prognostic value of m⁶A-related lncRNAs in hepatocellular carcinoma (HCC).

Methods: The m⁶A-related lncRNAs were identified based on the correlation coefficients with m⁶A-related genes in HCC from The Cancer Genome Atlas. Subsequently, a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate Cox analyses were used to identify independent prognostic factors for overall survival (OS) of HCC; thereafter, a prognostic nomogram was constructed.

Results: A total of 259 lncRNAs showed significant correlations with m⁶A in HCC, while 29 lncRNAs had prognostic significance. Further, six critical m⁶A-related lncRNAs (NRAV, SNHG3, KDM4A-AS1, AC074117.1, AC025176.1, and AL031985.3) were screened out to construct a novel risk score model which classified HCC patients into high- and low-risk groups. Survival analyses revealed that patients in the high-risk group exhibited worse OS, both in the training and validation groups. The risk score was also identified as an independent prognostic factor of OS, and a nomogram was established and verified with superior prediction capacity. Besides, the risk score significantly correlated with the expression of immune checkpoint genes and immune subtypes.

Conclusions: These findings indicated the significant role of m⁶A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.

Keywords: Hepatocellular carcinoma; Immune checkpoints; Long noncoding RNAs; N6-methyladenosine; Prognosis.