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

Yanping Tao¹Lei Zhong¹Qihua Shen²Xiaofan Zhang¹Xuyun Xu^1*Runlin Feng^3*

• ¹department of Emergency Medicine, Kunming Third People's Hospital, Kunming, China
• ²Department of Hepato-Pancreato-Biliary Surgery, Huzhou Central Hospital, Huzhou, China
• ³Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

Mitochondrial dysfunction has been increasingly implicated in the pathogenesis of primary biliary cholangitis (PBC), yet the specific roles of mitochondria-related genes (MRGs) in PBC remain poorly understood. This study aimed to identify key MRGs associated with PBC and validate their expression at both the transcriptional and protein levels. Blood samples from PBC patients and healthy controls were collected for transcriptome sequencing, with MRGs obtained from the MitoCarta 3.0 database. After quality control and preprocessing, differentially expressed genes (DEGs) were identified through comparative analysis of PBC and control groups. Key genes associated with PBC pathology were extracted using weighted gene co-expression network analysis (WGCNA). SHANK2 and TGM2 were identified as hub genes, showing AUC values greater than 0.7, and their expression was significantly higher in PBC patients. Enrichment analysis revealed that SHANK2 was associated with B cell receptor, T cell receptor, and Wnt signaling pathways, while TGM2 was linked to oxidative phosphorylation, pyrimidine metabolism, and purine metabolism. Immune cell analysis demonstrated significant differences between PBC and control groups, with certain immune cell types correlating with hub gene expression. A regulatory network analysis showed that SHANK2 and TGM2 were regulated by several key molecules, including SLFN12L and DNAH10OS. Additionally, immunohistochemistry confirmed elevated protein expression of SHANK2 and TGM2 in the liver tissues of PBC patients, with stage-specific increases, and RT-qPCR validated the higher mRNA expression of these genes in peripheral blood. Furthermore, disease correlation and drug prediction analyses indicated that SHANK2 and TGM2 could be potential targets for therapeutic intervention. Overall, this study identifies SHANK2 and TGM2 as key MRGs involved in the pathogenesis of PBC, providing novel insights into the link between mitochondrial dysfunction and immune dysregulation. These genes may serve as potential diagnostic biomarkers and therapeutic targets for PBC.