Abstract
Liver cancer (LC) is the fourth leading cause of cancer-related deaths worldwide. There is an urgent need to identify novel and reliable prognostic biomarkers for LC in order to improve patient outcomes. N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA and has been associated with various cancers, although its roles in the prognosis of LC remains to be elucidated. We analyzed the expression profiles of 15 m6A-related genes in the International Cancer Genome Consortium (ICGC) LIRI-JP dataset, and applied consensus clustering to stratify LC patients into two subgroups (Cluster 1 and Cluster 2). Cluster1 was significantly correlated to lower tumor stage and longer overall survival (OS). Gene set enrichment analysis showed that tumorigenic markers, including DNA repair, E2F targets, G2M checkpoint, and MYC targets V1, were enriched in Cluster2. We then constructed a prognostic risk model using three m6A-related genes that were identified as independent factors affecting OS. The nomogram based on the risk model score indicated good performance in predicting the 1-, 2- and 3-year survival of the LC patients. In conclusion, m6A-related genes are potential prognostic markers and therapeutic targets for LC.
Highlights
Liver cancer (LC) is the fourth leading cause of cancer-related deaths worldwide (Villanueva, 2019)
We analyzed the correlation among m6A-related genes
Numerous genes and non-coding RNAs associated with LC progression have been identified in recent years (Tsuei et al, 2004; Yuan et al, 2014; Chua et al, 2015; Li et al, 2016; Mattu et al, 2016; Xiao et al, 2016; Zhang et al, 2016; Liu et al, 2017; Zhao et al, 2018; Zhou et al, 2019), the prognosis of the patients remains disappointing
Summary
Liver cancer (LC) is the fourth leading cause of cancer-related deaths worldwide (Villanueva, 2019). The etiology of LC differs geographically due to differences in the prevalence of risk factors (Jiang et al, 2019). Chronic viral hepatitis infection is the most important risk factor in Asian countries, whereas non-viral factors are the major causative agents of LC in the Western countries (Yau et al, 2019). N6-methyladenosine (m6A), the most common internal post-transcriptional modification in eukaryotic mRNA, associates with many biological processes such as stress responses, stem cell differentiation, gametogenesis, and T Cell Homeostasis (Liu et al, 2019b; Zhou et al, 2019), and is mediated by factors that mainly include the “writers”
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