Identification of significant modules and hub genes involved in hepatic encephalopathy using WGCNA

Hepatic encephalopathy (HE) is a reversible syndrome of brain dysfunction caused by advanced liver disease. Weighted gene co-expression network analysis (WGCNA) could establish a robust co-expression network to identify the hub genes and underlying biological functions. This study was aimed to explore the potential therapeutic targets in HE by WGCNA.

The green and brown modules were found to be significantly associated with the development of HE. Functional enrichment analyses suggested the neuroinflammation, neuroimmune, extracellular matrix (ECM), and coagulation cascade were involved in HE. CYBB and FOXO1 were calculated as hub genes, which were upregulated in the HE patients. Tamibarotene and vitamin E were suggested as possible drug candidates to alleviate HE.

It is the first time to analyze transcriptomic data of HE by WGCNA. Our study not only promoted the current understanding of neuroinflammation in HE, but also provided the first evidence that CYBB and FOXO1 played pivotal roles in the pathogenesis of HE, which might be potential biomarkers and therapeutic targets. Tamibarotene might be a novel drug compound against HE.