Exploring novel prognostic biomarkers and biologic processes involved in NASH, cirrhosis and HCC based on survival analysis using systems biology approach

TL;DR

This study identifies novel biomarkers and biological processes involved in NASH, cirrhosis, and HCC using survival analysis and systems biology, aiming to improve therapeutic strategies.

Contribution

It introduces new candidate genes and key pathways associated with disease progression based on in silico survival analysis, which were not previously characterized.

Findings

Identified specific upregulated genes in NASH, cirrhosis, and HCC.

Found 4 common genes across all three conditions, with YWHAZ linked to poor survival.

Detected new candidate biomarkers and biological processes for further validation.

Abstract

There is an unmet need to develop medications or drug combinations which can stop advancement of NASH to liver cirrhosis and HCC. Therefore, identifying key biomarkers based on overall survival and the exploring biological processes involved in the pathogenesis and progression of NASH toward cirrhosis and HCC to improve therapeutic interventions is necessary. The microarray dataset from the GPL13667 platform was downloaded from the Gene Expression Omnibus (GEO). The inclusion criteria for the DEGs included an adjusted p-value <0.05 and a log(2) fold change >1. In the first step, protein-protein interaction (PPI) network of differentially expressed genes (DEGs) in every three groups (NASH, Cirrhosis and HCC) was constructed using STRING online database. In the second step, the DEGs of each group were imported to Cytoscape software separately, and the genes with Degree >3 were selected. In the third step, the genes with Degree >3 were imported to Gephi software (0.9.2 version) and the genes with betweenness centrality >0 were selected. Venn diagram of these genes was depicted for the NASH, cirrhotic and HCC groups. According to venn diagram, 96 (NASH), 30 (cirrhotic) and 213 (HCC) genes were specifically upregulated (based on inclusion criteria). Among specific genes, 22 (NASH), 5 (cirrhotic) and 82 (HCC) genes were with poor overall survival. The overlap among the 3 groups (NASH, Cirrhosis and HCC) contained 4 upregulated genes HLA-F, HLA-DPA1, TPM1 and YWHAZ. From 4 upregulated genes, only YWHAZ gene was with poor overall survival. The present study detected new candidate genes and key biological processes in NASH, cirrhosis and HCC based on overall survival and using in silico analysis. Therefore, performing in vitro and in vivo researches to verify the results is necessary.