Development and Validation of Epigenetic Modification-Related Signals for the Diagnosis and Prognosis of Hepatocellular Carcinoma

Abstract

BackgroundIncreasing evidence has indicated that abnormal epigenetic factors such as RNA m6A modification, histone modification, DNA methylation, RNA binding proteins and transcription factors are correlated with hepatocarcinogenesis. However, it is unknown how epigenetic modification-associated genes contribute to the occurrence and clinical outcome of hepatocellular carcinoma (HCC). Thus, we constructed the epigenetic modification-associated models that may enhance the diagnosis and prognosis of HCC.MethodsIn this study, we focused on the clinical value of epigenetic modification-associated genes for HCC. Our gene expression data were collected from TCGA and HCC data sets from the GEO database to ensure the reliability of the data. Their functions were analyzed by bioinformatics methods. We used lasso regression, Support vector machine (SVM), logistic regression and Cox regression to construct the diagnostic and prognostic models. We also constructed a nomogram of the practicability of the above-mentioned prognostic model. The above results were verified in an independent liver cancer data set from the ICGC database and clinical samples. Furthermore, we carried out pan-cancer analysis to verify the specificity of the above model and screened a wide range of drug candidates.ResultsMany epigenetic modification-associated genes were significantly different in HCC and normal liver tissues. The gene signatures showed a good ability to predict the occurrence and survival of HCC patients, as verified by DCA and ROC curve analysis.ConclusionGene signatures based on epigenetic modification-associated genes can be used to identify the occurrence and prognosis of liver cancer.

Does Chronic Kidney Disease Really Affect the Complications and Prognosis After Liver Resection for Hepatocellular Carcinoma? A Meta-Analysis

“…There are many factors that could affect the prognosis after liver resection for HCC including presence of vascular penetration, satellite nodules, tumor differentiation, hepatitis, cirrhosis, and tumor staging ( 32 , 33 ). In this meta-analysis, the CKD group had poor OS compared with the non-CKD group; however, in terms of DFS, no significant difference was found.…”

Role of m6A RNA methylation in the development of hepatitis B virus‐associated hepatocellular carcinoma

“…In view of the diverse biological effects of m6A modification on the development of HBV‐associated HCC, m6A methylation is expected to be used in the diagnosis, treatment, and prognosis of HBV‐associated HCC 137,138 …”

“…In view of the diverse biological effects of m6A modification on the development of HBV-associated HCC, m6A methylation is expected to be used in the diagnosis, treatment, and prognosis of HBV-associated HCC. 137,138 m6A methylation can be used as tumor biomarkers for the diagnosis of HBV-associated HCC. ALKBH5 has the highest expression in HBV-HCC tissues compared with moderate expression in paracancerous tissues and the lowest expression in normal liver tissues.…”

Advances in RNA Epigenetic Modifications in Hepatocellular Carcinoma and Potential Targeted Intervention Strategies

“…With the deepening of research, some previously unknown RNA binding proteins, such as nuclear factor κB (NF-κB)-related protein (NKAP) and heterogeneous nuclear protein (HNRNP) families (HNRNPA2B1, HNRNPG, and HNRNPC), have also been identified via particular m6A identification to be able to assist the m6A process to affect the RNAs' fate as well as their functions exhibited by cells (Zaccara et al, 2019). Increasing evidence shows that the total m6A level and its regulators in HCC tissue have abnormal changes and are closely related to poor clinical prognosis (Lu et al, 2021;Xu et al, 2021). Furthermore, m6A-modified regulators exert a carcinogenic or antitumor effect in HCC by affecting the expression of certain specific genes (Li et al, 2021).…”