Multi-omics data identified TP53 and LRP1B as key regulatory gene related to immune phenotypes via EPCAM in HCC

Many studies showed that the prognosis of hepatocellular carcinoma (HCC) was significantly associated with the expressions of TP53 and LRP1B. However, the potential influence of the two genes on the malignant progression of HCC is still to be expounded.

According to the correlation analysis between immune cells and expression levels of TP53 and LRP1B, we filtered the immune cells to perform unsupervised clustering analysis. Integration of multi-omic data analysis identified genetic alteration and epigenetic alteration. In addition, pathway analysis was used to explore the potential function of the differentially expressed mRNAs. According to the differentially expressed genes, we established an interaction network to seek the hub gene. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a prognosis model.

The unsupervised clustering analysis showed that the cluster A1 showed the highest immune cell levels and the cluster B2 showed the lowest immune cell levels. Multi-omics data analysis identified that somatic mutations, copy number variations, and DNA methylation levels had significant differences between cluster A1 and cluster B2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the upregulated mRNAs in the cluster A1 were mainly concentrated in T cell activation, external side of plasma membrane, receptor ligand activity, and cytokine-cytokine receptor interaction. Importantly, the EPCAM was identified as a critical node in the lncRNAs-miRNAs-mRNAs regulatory network correlated with the immune phenotypes. In addition, based on differentially expressed genes between cluster A1 and cluster B2, the prognostic model established by LASSO could predict the overall survival (OS) of HCC accurately.

The results indicated that the TP53 and LRP1B acted as the key genes in regulating the immune phenotypes of HCC via EPCAM.