OBJECTIVE: The crosstalk between Toll-like receptor 4 (TLR-4) and lipopolysaccharide (LPS) accounts for liver fibrosis progression. This study aimed to investigate the predictive performance of altered genes induced by TLR-4 and LPS challenge for advanced liver fibrosis.
MATERIALS AND METHODS: The overlapping differentially expressed genes (DEGs) of TLR-4 and LPS challenge models from the Gene Expression Omnibus (GEO) database were screened and included in the random forest analysis to identify potential candidates for predicting advanced liver fibrosis in the GSE84044 dataset. The roles of the identified candidates in liver injury development and activation of hepatic stellate cells (HSCs) were also addressed.
RESULTS: Among the overlapping DEGs in the GSE30485, GSE33446 and GSE166488 datasets, vimentin (VIM) was the most important gene for predicting advanced liver fibrosis (S ≥ 2) by the random forest model. In the GSE84044 dataset, VIM was positively correlated with liver fibrosis (r = 0.68, 95% CI = 0.57-0.76, p < 0.0001), and accurately predicted advanced liver fibrosis (AUC = 0.85, 95% CI = 0.78-0.91), both in males (AUC = 0.84, 95% CI = 0.76-0.92) and females (AUC = 0.87, 95% CI = 0.76-0.99). VIM was significantly upregulated in various liver diseases (cirrhosis, liver failure, chronic hepatitis B and fatty liver disease) and liver injury models (ANIT, BDL, CCl4 and DMN). Additionally, VIM was correlated with HSC regulators (TGFβ, PDGF, CTGF and BMP7) and overexpressed in activated HSCs (p < 0.05). Enrichment analysis indicated that VIM-induced gene alterations were involved in the cytosolic DNA-sensing pathway, Toll-like receptor signaling pathway, etc.
CONCLUSIONS: VIM could predict advanced liver fibrosis in CHB patients and is mainly involved in the activation of HSCs and profibrotic signaling pathways.Free PDF Download
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To cite this article
W.-M. Wang, W.-S. Zhang, Z.-G. Yang
Vimentin (VIM) predicts advanced liver fibrosis in chronic hepatitis B patients: A random forest-derived analysis
Eur Rev Med Pharmacol Sci
Vol. 26 - N. 14