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In Heliyon

Background : Patients with mid-stage HCC (hepatocellular carcinoma) may benefit from transcatheter arterial chemoembolization (TACE). However, patient efficacy varies widely, and the detailed assessment index is unknown. The most general methylation alteration in mRNA (Messenger RNA), N6-methyladenosine (m6A), is controlled by the m6A regulator, which is associated with the emergence of tumors. To include the molecular causes of cancer, competition with ceRNA (endogenous RNA) networks is crucial. However, the exact processes they contribute to TACE HCC remain uncertain. The purpose of this study was tantamount to investigating the possible function of ceRNA networks and m6A regulators in patients with TACE HCC.

Methods : Genes Associated with m6A were discovered using the TACE GEO (Gene Expression Omnibus) dataset. An additional estimate of M6A-associated DEGs (differentially expressed genes) was used to create a predictive response model, which is required. LncRNA-miRNA and miRNA-mRNA interactions were then predicted, the regulatory ceRNA network was set up using Cytoscape software, and target genes were identified using GEPIA online analysis. The connection between immunological checkpoints, immune cell marker genes, and target genes for immune cells was also examined.

Results : The detection of 4 m6A-associated DEGs, the development and evaluation of 2 Machine learning models, and the development of risk models that accurately predicted the response rate of specific patients. Additionally, we obtained two miRNAs (micro RNAs)and six lncRNAs (Long non-coding RNAs), forming an 8-pair ceRNA network, and the target gene LRPPRC deletion of one copy number and gene expression was highly correlated with the amount of Tregs immune cells. LRPPRC was related positively with NRP1, IRF5, and ITGAM and negatively with CCR7 and CD8B among immune cell marker genes. We also discovered that LRPPRC correlates positively with immune checkpoint CD274 cells.

Conclusion : The response of HCC patients to TACE therapy may be predicted using a model based on four gene expression data. We also developed a ceRNA network for TACE HCC related to m6A, which offered suggestions for more research into its molecular processes and possible prognostic indicators.

Huang Deliang, Huang Dejing

2022-Oct

HCC, TACE, ceRNA network, m6A