Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
Department of Endocrinology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, 215300, China.
Endocr Metab Immune Disord Drug Targets. 2023;23(9):1173-1185. doi: 10.2174/1871530323666221208105720.
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.
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.
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.
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.
免疫细胞浸润是非酒精性脂肪性肝病（NAFLD）发病机制的一个重要组成部分。本研究旨在探索与 NAFLD 进展相关的免疫浸润的新基因。
通过高通量测序数据集，使用 CIBERSORT 评估人类 NAFLD 中免疫浸润的丰度。进一步进行加权基因共表达网络分析（WGCNA），以搜索与差异免疫细胞相关的易感基因模块和枢纽基因。还探索了枢纽基因在不同肝非实质细胞簇和与 NAFLD 相关的肝细胞癌（HCC）中的表达。
最终确定了 4 个枢纽基因（ITGBL1、SPINT1、COL1A2 和 THBS2），它们可能与免疫浸润、纤维化进展和活动评分有关。接收器操作特征曲线（ROC）分析表明，这些基因对 NASH 和晚期纤维化具有良好的预测价值。单细胞分析表明，COL1A2 在肝星状细胞（HSCs）中高表达，尤其是在晚期，而 SPINT1 在胆管细胞（Cho）中高表达。此外，ITGBL1、COL1A2 和 THBS2 可能与从非酒精性脂肪性肝炎（NASH）向 HCC 的转化有关。我们的研究结果确定了几个可能与 NAFLD 免疫浸润相关的新基因。
这些基因可能作为评估免疫浸润的潜在标志物以及 NAFLD 的治疗靶点。需要进一步的研究来阐明这些基因在 NAFLD 发生和发展中的生物学机制。
