Gene signatures and prognostic values of m1A-related regulatory genes in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) ranks fourth in cancer-related mortality worldwide. N1-methyladenosine (m1A), a methylation modification on RNA, is gaining attention for its role across diverse biological processes. However, m1A-related regulatory genes expression, its relationship with clinical prognosis, and its role in HCC remain unclear. In this study, we utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to investigate alterations within 10 m1A-related regulatory genes and observed a high mutation frequency (23/363). Cox regression analysis and least absolute shrinkage and selection operator were used to explore the association between m1A-related regulatory genes expression and HCC patient survival and identified four regulators that were remarkably associated with HCC patient prognosis. Additionally, an independent cohort from International Cancer Genome Consortium was studied to validate our discoveries and found to be consistent with those in the TCGA dataset. In terms of mechanism, gene set enrichment analysis linked these four genes with various physiological roles in cell division, the MYC pathway, protein metabolism, and mitosis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that PI3K/Akt signaling pathway had potential relevance to m1A-related regulatory genes in HCC. These findings indicate that m1A-related regulatory genes may play crucial roles in regulating HCC progression and be exploited for diagnostic and prognostic purposes.

Genetic characteristics and prognostic implications of m1A regulators in pancreatic cancer

“…Therefore, we speculated that the genes may differ in tumors, providing clues for the study of pancreatic cancer. Especially the prognostic model of m1A in liver cancer has been established [ 14 ]. As far as our research is concerned, the fact is that the overexpression of ALKBH1 is negatively correlated with the clinical stage of pancreatic cancer and is associated with a good prognosis.…”

“…For example, there is a significant relationship between changes in gene markers and clinical characteristics in the progression of clear cell renal cell carcinoma [ 13 ]. In addition, there has also been increased interest in the study of the RNA methylation modifications N1 methyladenosine (m1A) [ 14 ] and 5-methylcytosine (m5C) [ 15 ].…”

Recent advances in functional annotation and prediction of the epitranscriptome

“…Using similar pipeline, many studies have revealed the diagnostic and prognostic roles of m 6 A or other methylation (e.g., m 1 A) regulators in specific cancer including but not limited to hepatocellular carcinoma [162] , [163] , uveal melanoma [164] , prostate cancer [165] , gynecological cancers [166] , esophageal cancer [167] , thyroid carcinoma [168] and renal carcinoma [169] . Moreover, Meng et al have built the m 6 A-related mRNA signature to predict the prognosis of pancreatic cancer patients [170] and predicted that PAH, ZPLD1, PPFIA3, and TNNT1 genes exhibited an independent prognostic value using correlation and survival analysis.…”

m5C RNA Methylation Regulators Predict Prognosis and Regulate the Immune Microenvironment in Lung Squamous Cell Carcinoma

“…A recent study has shown that m5C also played an important role under pathological conditions ( 13 ), such as in cancer; NSUN2 and YBX1 promoted pathogenesis in human bladder urothelial carcinoma by targeting the m5C methylation site in the untranslated region of HDGF3 . Adding a methyl group to the N1 position of adenosine will form an m1A, which appears mainly upstream of the initiation codon of the first splicing site and has a strong enrichment effect on translation in the 5’UTR ( 14 ). However, little is known about the function of m5C and m1A regulators in NSCLC.…”