Integrative bioinformatics analysis and experimental validation of key biomarkers for risk stratification in primary biliary cholangitis

医学 原发性胆汁性肝硬化 熊去氧胆酸 内科学 生物信息学 原发性硬化性胆管炎 基因表达谱 疾病 基因 肿瘤科 计算生物学 基因表达 生物 遗传学
作者
Siyuan Tian,Yinan Hu,Miao Zhang,K. Wang,Guanya Guo,Bo Li,Yulong Shang,Ying Han
出处
期刊:Arthritis Research & Therapy [BioMed Central]
卷期号:25 (1) 被引量:3
标识
DOI:10.1186/s13075-023-03163-y
摘要

Primary biliary cholangitis (PBC) is an autoimmune liver disease, whose etiology is yet to be fully elucidated. Currently, ursodeoxycholic acid (UDCA) is the only first-line drug. However, 40% of PBC patients respond poorly to it and carry a potential risk of disease progression. So, in this study, we aimed to explore new biomarkers for risk stratification in PBC patients to enhance treatment.We first downloaded the clinical characteristics and microarray datasets of PBC patients from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Hub genes were further validated in multiple public datasets and PBC mouse model. Furthermore, we also verified the expression of the hub genes and developed a predictive model in our clinical specimens.A total of 166 DEGs were identified in the GSE79850 dataset, including 95 upregulated and 71 downregulated genes. Enrichment analysis indicated that DEGs were significantly enriched in inflammatory or immune-related process. Among these DEGs, 15 risk-related genes were recognized and further validated in the GSE119600 cohort. Then, TXNIP, CD44, ENTPD1, and PDGFRB were identified as candidate hub genes. Finally, we proceeded to the next screening with these four genes in our serum samples and developed a three-gene panel. The gene panel could effectively identify those patients at risk of disease progression, yielding an AUC of 0.777 (95% CI, 0.657-0.870).In summary, combining bioinformatics analysis and experiment validation, we identified TXNIP, CD44, and ENTPD1 as promising biomarkers for risk stratification in PBC patients.
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