Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation
BackgroundGlutathione peroxidase 3 (GPX3) is a strong antioxidant. While elevated GPX3 levels are linked to diverse pathologies, its role in liver failure (LF) remains underexplored. This study investigates GPX3’s diagnostic potential and mechanistic contributions to LF pathogenesis.MethodsWe integr...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1554116/full |
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| author | Quan Ye Kai Wang Hong Ye |
| author_facet | Quan Ye Kai Wang Hong Ye |
| author_sort | Quan Ye |
| collection | DOAJ |
| description | BackgroundGlutathione peroxidase 3 (GPX3) is a strong antioxidant. While elevated GPX3 levels are linked to diverse pathologies, its role in liver failure (LF) remains underexplored. This study investigates GPX3’s diagnostic potential and mechanistic contributions to LF pathogenesis.MethodsWe integrated two high-quality liver tissue datasets (GSE38941 and GSE14668) from the Gene Expression Omnibus (GEO) database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to identify potential biomarkers associated with liver failure. The Comparative Toxicogenomics Database was used to predict the function of GPX3. In addition, in our study, we verified the target gene mRNA expression level in 40 patients with acute or chronic acute liver failure (ACHBLF) by RT-QCPR experiment and detect the methylation status of GPX3 promoter of ACHBLF patients with methylation specific PCR (MSP).ResultsThe results demonstrate that GPX3 drives pathogenic mechanisms in liver failure through oxidative stress-related pathways (e.g., collagen cross-linking, extracellular matrix remodeling) and immune dysregulation (e.g., macrophage activation, PD-1/CTLA-4 signaling). CPX8, PRDX6, GPX4, GSS, GSR, TXN, GPX7, PPARGC1A, ALOX15, and ALOX5 have been identified as key immune-related genes. Furthermore, there were significant differences in immune cell infiltration between the high and low expression groups of GPX3 groups. Immune infiltration analysis demonstrated strong correlations between GPX3 expression and key immune markers (p < 0.05), suggesting its role in modulating inflammatory responses. Additionally, GPX3 increased susceptibility to aerosols, cyclosporin and dexamethasone was observed in patients with elevated levels of GPX3. The mRNA expression of GPX3 was much higher in ACHBLF patients than in other groups. In ACHBLF patients, the group with GPX3 methylated promoter had higher mortality than those without.ConclusionIn conclusion, GPX3 is a promising diagnostic biomarker for liver failure. Its promoter methylation status may serve as a prognostic indicator, highlighting its therapeutic potential. |
| format | Article |
| id | doaj-art-93f2e300cc304b64b4c879690059e44a |
| institution | OA Journals |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-93f2e300cc304b64b4c879690059e44a2025-08-20T02:11:34ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-04-011610.3389/fgene.2025.15541161554116Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validationQuan Ye0Kai Wang1Hong Ye2Clinical Laboratory Department, Tongji University Affiliated East Hospital Jiaozhou Hospital, Jiaozhou, Shandong, ChinaLiver Disease Research Institute, Shandong University, Jinan, Shandong, ChinaDigestive Endoscopy Center, Tongji University Affiliated East Hospital Jiaozhou Hospital, Jiaozhou, Shandong, ChinaBackgroundGlutathione peroxidase 3 (GPX3) is a strong antioxidant. While elevated GPX3 levels are linked to diverse pathologies, its role in liver failure (LF) remains underexplored. This study investigates GPX3’s diagnostic potential and mechanistic contributions to LF pathogenesis.MethodsWe integrated two high-quality liver tissue datasets (GSE38941 and GSE14668) from the Gene Expression Omnibus (GEO) database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to identify potential biomarkers associated with liver failure. The Comparative Toxicogenomics Database was used to predict the function of GPX3. In addition, in our study, we verified the target gene mRNA expression level in 40 patients with acute or chronic acute liver failure (ACHBLF) by RT-QCPR experiment and detect the methylation status of GPX3 promoter of ACHBLF patients with methylation specific PCR (MSP).ResultsThe results demonstrate that GPX3 drives pathogenic mechanisms in liver failure through oxidative stress-related pathways (e.g., collagen cross-linking, extracellular matrix remodeling) and immune dysregulation (e.g., macrophage activation, PD-1/CTLA-4 signaling). CPX8, PRDX6, GPX4, GSS, GSR, TXN, GPX7, PPARGC1A, ALOX15, and ALOX5 have been identified as key immune-related genes. Furthermore, there were significant differences in immune cell infiltration between the high and low expression groups of GPX3 groups. Immune infiltration analysis demonstrated strong correlations between GPX3 expression and key immune markers (p < 0.05), suggesting its role in modulating inflammatory responses. Additionally, GPX3 increased susceptibility to aerosols, cyclosporin and dexamethasone was observed in patients with elevated levels of GPX3. The mRNA expression of GPX3 was much higher in ACHBLF patients than in other groups. In ACHBLF patients, the group with GPX3 methylated promoter had higher mortality than those without.ConclusionIn conclusion, GPX3 is a promising diagnostic biomarker for liver failure. Its promoter methylation status may serve as a prognostic indicator, highlighting its therapeutic potential.https://www.frontiersin.org/articles/10.3389/fgene.2025.1554116/fullglutathione peroxidase 3hepatic failureimmune cell infiltrationpromoter methylationdiagnostic biomarker |
| spellingShingle | Quan Ye Kai Wang Hong Ye Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation Frontiers in Genetics glutathione peroxidase 3 hepatic failure immune cell infiltration promoter methylation diagnostic biomarker |
| title | Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation |
| title_full | Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation |
| title_fullStr | Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation |
| title_full_unstemmed | Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation |
| title_short | Liver failure diagnosis: key diagnostic biomarkers discovery and bioinformatic validation |
| title_sort | liver failure diagnosis key diagnostic biomarkers discovery and bioinformatic validation |
| topic | glutathione peroxidase 3 hepatic failure immune cell infiltration promoter methylation diagnostic biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1554116/full |
| work_keys_str_mv | AT quanye liverfailurediagnosiskeydiagnosticbiomarkersdiscoveryandbioinformaticvalidation AT kaiwang liverfailurediagnosiskeydiagnosticbiomarkersdiscoveryandbioinformaticvalidation AT hongye liverfailurediagnosiskeydiagnosticbiomarkersdiscoveryandbioinformaticvalidation |