Exploring key biomarkers of liver fibrosis progression to hepatocellular carcinoma based on immune cell-related genes

Background: Disturbance of the immune microenvironment was critical throughout the development of hepatic fibrosis (HF) to cirrhosis and induction of hepatocellular carcinoma (HCC). It is essential to explore the key biomarkers which related to immune and investigate a potential target of diagnosis and immunological therapy in the progression of HF to HCC. Methods: The GSE89377, GSE63898, GSE84044 and The Cancer Genome Atlas (TCGA) TCGA-HCC datasets were enrolled to screen common differentially expressed genes (co-DEGs) which in HF, cirrhosis and HCC. The functions and metabolic pathways of co-DEGs were explored and analyzed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Besides, the gene set variation analysis (GSVA) in the GSE89377 dataset was employed to identify differential immune cells and prognosis-related differential immune cells were obtained by survival analysis. Subsequently, least absolute shrinkage and selection operator (LASSO) and Boruta for getting biomarkers on the basis of candidate genes which screening through the correlation analysis. Whereafter, the biomarkers which related to differential immune cells were getting from the single-gene set enrichment analysis (GSEA). Lastly, a biomarkers-drug network was established. Results: In total, 30 co-DEGs were obtained which were involved in cholesterol homeostasis and complement and coagulation cascades. 6 prognosis-related differential immune cells and 14 candidate genes were screened. The correlation analysis showed that lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) and myeloid cell leukemia 1 (MCL-1) were identified as biomarkers. 47 miRNAs, 67 lncRNAs and 2 biomarkers were encompassed in the ceRNA regulatory network, 47 drugs targeting MCL-1 were predicted using biomarker-drug network finally. Conclusion: A series of altered immune cell and the signaling pathways that were closely correlated were crucial in immune mechanism during HF developing into HCC. LYVE1 and MCL-1 might as potential key biomarkers based on immune- associated genes, which will provide new insights into the treatment for preventing the progression of HF to HCC.