Work

The role of mitochondria-related key genes in primary biliary cholangitis was analyzed based on transcriptome sequencing data

Year: 2025

Type: article

Abstract: Introduction: Mitochondrial dysfunction is implicated in the pathogenesis of primary biliary cholangitis (PBC), but the roles of mitochondria-related genes (MRGs) remain unclear. We aimed to identify key MRGs associated with PBC and validate their expression at transcriptional and protein levels. Methods: Peripheral blood from PBC patients and healthy controls underwent RNA-seq. MRGs were sourced from MitoCarta 3.0. After quality control, differentially expressed genes were defined between PBC and controls and integrated with weighted gene co -expression network analysis to obtain candidate genes. LASSO and SVM-RFE selected hub genes, whose diagnostic performance was assessed by ROC in both the discovery cohort and an external validation dataset. Functional enrichment, immune-cell composition analyses, and regulatory network construction (miRNA/lncRNA/TF) were performed. Protein and mRNA expression were validated by liver -tissue immunohistochemistry and peripheral-blood RT-qPCR, respectively. Disease correlation and drug-prediction analyses were conducted. Results: SHANK2 and TGM2 were identified as hub MRGs, showed higher expression in PBC, and achieved AUC values >0.7. Enrichment linked SHANK2 to Bcell receptor, T-cell receptor, and Wnt signaling pathways, while TGM2 associated with oxidative phosphorylation and nucleotide metabolism. Immune-cell profiles differed between PBC and controls, and selected cell types correlated with hub-gene expression. Regulatory analyses suggested modulation of SHANK2 and TGM2 by molecules including SLFN12L and DNAH10OS. Immunohistochemistry revealed elevated, stage-associated protein expression of both genes in PBC liver tissues, and RT-qPCR confirmed higher peripheralblood mRNA levels. Drug/disease analyses indicated therapeutic potential for targeting these genes. Discussion: SHANK2 and TGM2 emerge as key MRGs linking mitochondrial dysfunction with immune dysregulation in PBC and may serve as diagnostic biomarkers and therapeutic targets; further mechanistic and clinical validation is warranted.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2025.1644682

Authors: Yanping Tao, Lei Zhong, Qihua Shen, Xiaofan Zhang, Xuyun Xu, Runlin Feng

Institutions: Kunming Third People's Hospital, Huzhou Central Hospital, Kunming Medical University

Language: English

Topic: Liver Diseases and Immunity

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801