Diagnostic and prognostic value of m5C regulatory genes in hepatocellular carcinoma

Abstract

Background: A high mortality rate makes hepatocellular carcinoma (HCC) one of the most common types of cancer globally. 5-methylcytosine (m5C) is an epigenetic modification that contributes to the prognosis of several cancers, but its relevance to HCC remains unknown. We sought to determine if the m5C-related regulators had any diagnostic or prognostic value in HCC.Methods: M5C regulatory genes were screened and compared between HCC and normal tissue from The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. Least absolute shrinkage and selection operator method (LASSO) and univariate Cox regression analysis of differentially expressed genes were then performed to identify diagnostic markers. A LASSO prognostic model was constructed using M5C regulatory genes with prognostic values screened by TCGA expression data. HCC patients were stratified based on risk score, then clinical characteristics analysis and immune correlation analysis were performed for each subgroup, and the molecular functions of different subgroups were analyzed using both Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). The prognostic model was evaluated using univariate and multivariate Cox analyses as well as a nomogram. Molecular typing was performed according to m5C regulatory genes and immune checkpoint genes expression respectively, and clinical characterization and immune correlation analysis were performed for each subgroup.Results: M5C regulatory genes are expressed differently in HCC patients with different clinical and pathological characteristics, and mutations in these genes are frequent. Based on five m5C regulators (NOP2, NSUN2, TET1, YBX1, and DNMT3B), we constructed a prognostic model with high predictive ability. The risk score was found to be an independent prognostic indicator. Additionally, risk scores can also be applied in subgroups with different clinical characteristics as prognostic indicators.Conclusion: The study combined data from TCGA and GEO for the first time to reveal the genetic and prognostic significance of m5C-related regulators in HCC, which provides new directions for identifying predictive biomarkers and developing molecularly targeted therapies for HCC.

m1A regulator-mediated methylation modification patterns correlated with autophagy to predict the prognosis of hepatocellular carcinoma

“…The clinical usefulness of this study was validated in patients with HCC, indicating that this predictive pattern possesses significant diagnostic worth for 1-year, 3-year, and 5-year survival rates, the AUC values in the training cohort were 0.773, 0.699, 0.677. Models constructed based on m 6 A, m 7 G or m 5 C-related regulatory genes for the diagnosis in patients with HCC has been reported, the AUC values range from 0.61 to 0.74 [ 38 – 40 ]. However, so far, except for AFP, there is no single stand-alone biological indicator that has yet been identified as a biomarker for the diagnosis of HCC [ 41 ].…”

Genetic variants in m5C modification core genes are associated with the risk of Chinese pediatric acute lymphoblastic leukemia: A five-center case–control study

“…Several lines of data have introduced m5C modification as an important regulator in post-transcription. In the study of carcinogenesis, m5C-modified genes have been reported to be associated with a variety of cancers, including bladder cancer ( 19 ), hepatocellular carcinoma ( 20 ), glioblastoma multiforme ( 21 ), and leukemia ( 22 ). However, limited pieces of evidence have focused on the function of polymorphisms of m5C genes on disease susceptibility.…”

Identification and validation of a tyrosine metabolism-related prognostic prediction model and characterization of the tumor microenvironment infiltration in hepatocellular carcinoma

“…Recently, there are an increasing number of studies working on the prognostic model of HCC based on ferroptosis phenotypes ( 37 ), cuproptosis-related genes ( 38 ), m 5 C regulatory genes ( 39 ), hypoxia-related angiogenic genes ( 40 ), et al. They all showed meaningful clinical implications to some extent.…”