Weighted Gene Co-Expression Network Analysis of Immune Infiltration in Nonalcoholic Fatty Liver Disease

Abstract

Background: Immune cell infiltration is an important component of nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to explore novel genes associated with immune infiltration in the progression of NAFLD. Methods: CIBERSORT was used to evaluate the abundance of immune infiltration in the human NAFLD via a high-throughput sequencing dataset. Further weighted gene co-expression network analysis (WGCNA) was performed to search for the susceptibility gene module and hub genes associated with differential immune cells. The expression of hub genes in different liver non-parenchymal cell clusters and NAFLD-associated hepatocellular carcinoma (HCC) was also explored. Results: Four hub genes (ITGBL1, SPINT1, COL1A2, and THBS2) were ultimately identified, which may be associated with immune infiltration, fibrosis progression, and activity score. The receiver operating characteristic curve (ROC) analysis suggested that these genes had good predictive value for NASH and advanced fibrosis. A single-cell analysis showed that COL1A2 was highly expressed in hepatic stellate cells (HSCs), especially in the later stage, while SPINT1 was highly expressed in cholangiocytes (Cho). In addition, ITGBL1, COL1A2, and THBS2 might be associated with transforming from nonalcoholic steatohepatitis (NASH) to HCC. Our findings identified several novel genes that might be related to immune infiltration in NAFLD. Conclusion: These genes may serve as potential markers for the assessment of immune infiltration as well as therapeutic targets for NAFLD. More studies are needed to elucidate the biological mechanism of these genes in the occurrence and development of NAFLD.

Comprehensive meta-analysis reveals distinct gene expression signatures of MASLD progression

“…In individuals with chronic hepatitis B, ITGBL1 , which promotes cell migration ( 40 ), has been shown to regulate fibrogenesis ( 25 ) and is part of a six-gene signature predictive of cirrhosis ( 41 ). In a weighted gene coexpression network analysis (WGCNA) focused on susceptibility gene modules related to immune cells in MASLD, ITGBL1 was among the hub genes linked to immune infiltration, fibrosis progression, and activity score ( 42 ). LOXL1 , a member of the lysyl oxidase (LOX) family of enzymes involved in collagen and elastin crosslinking, has also been linked to liver cirrhosis ( 43 , 44 ).…”

Association of Systemic Immune-Inflammation Index with Non-Alcoholic Fatty Liver Disease: A Population-Based Cross-Sectional Study

“…Wang et al found that genes associated with immune infiltration may serve as potential markers for therapeutic targets for NAFLD. 39 Xie et al Revealed that a high SII index is associated with hepatic steatosis but not with liver fibrosis. 40 In addition, Song Y and his team also found that U.S. adults with a high SII index had an increased risk of hepatic steatosis.…”