Genomics · 2026
Integrated analysis of transcriptome and metabolome reveals key metabolites-related genes in chronic liver failure.
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Shu Faming, Huang Ying, Zhang Kan, Lin Yong, Li Jiongfen, Long Fuli, Mao Dewen, Wang Na
Аннотация
OBJECTIVES: To identify molecular biomarkers associated with chronic liver failure (CLF) progression to acute-on-chronic liver failure (ACLF).
METHODS: RNA-seq data from 8 CLF patients-stratified into high-severity (G, ACLF with total bilirubin ≥171 μmol/L) and low-severity (L, stable CLF with total bilirubin <171 μmol/L) groups-along with 4 healthy controls were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-associated gene modules.
RESULTS: A total of 3112 differentially expressed genes (DEGs) were identified, with KEGG analysis showing enrichment in innate immune pathways. Metabolomic profiling revealed 63 differentially expressed metabolites (DEMs), with four bile acids-Glycochenodeoxycholic acid, Glycocholic acid, Glycodeoxycholic acid, and Lithocholic acid-identified as key metabolites in bile acid biosynthesis pathways. Strong negative correlations were observed between these hydrophobic bile acids and 33 hub genes.
CONCLUSIONS: Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts.
METHODS: RNA-seq data from 8 CLF patients-stratified into high-severity (G, ACLF with total bilirubin ≥171 μmol/L) and low-severity (L, stable CLF with total bilirubin <171 μmol/L) groups-along with 4 healthy controls were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-associated gene modules.
RESULTS: A total of 3112 differentially expressed genes (DEGs) were identified, with KEGG analysis showing enrichment in innate immune pathways. Metabolomic profiling revealed 63 differentially expressed metabolites (DEMs), with four bile acids-Glycochenodeoxycholic acid, Glycocholic acid, Glycodeoxycholic acid, and Lithocholic acid-identified as key metabolites in bile acid biosynthesis pathways. Strong negative correlations were observed between these hydrophobic bile acids and 33 hub genes.
CONCLUSIONS: Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts.