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

Zhaoxiang      Wang; Yue      Xia; Yi      Pan; Li      Zhang; Fengyan      Tang; Xiawen      Yu; Zhongming      Yang; Dong      Wang; Ling      Yang; Jue      Jia; Guoyue      Yuan

doi:10.2174/1871530323666221208105720

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.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1871530323666221208105720	Print ISSN 1871-5303
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Endocrine, Metabolic & Immune Disorders - Drug Targets

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

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