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Proteomics Defines Plasma Biomarkers for the Early Diagnosis of Biliary Atresia
Ming Fu1, Zhipeng Guo1, Yan Chen1,2
1Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China.
Insights
Early diagnosis of biliary atresia (BA) is vital for pediatric liver health. Proteomics identified a novel plasma biomarker combination for accurate early BA detection, improving patient outcomes.
Area of Science:
- Biochemistry
- Pediatric Gastroenterology
- Proteomics
Background:
- Biliary atresia (BA) is a serious pediatric liver condition requiring early diagnosis for effective treatment.
- Current diagnostic methods can be invasive or lack specificity, highlighting the need for improved early detection strategies.
Purpose of the Study:
- To identify novel plasma biomarkers for the early diagnosis of biliary atresia (BA) in pediatric patients.
- To differentiate BA from other causes of neonatal jaundice using proteomic analysis.
Main Methods:
- Proteomics analysis using data-independent acquisition (DIA) and parallel reaction monitoring (PRM) on patient plasma samples.
- Bioinformatics and signaling pathway analysis to identify differentially expressed proteins and biological processes.
- Machine learning models were employed to develop a diagnostic panel.
Main Results:
- Differential protein expression was detected and validated in the plasma of BA patients compared to those with intrahepatic cholestasis.
- Signaling pathway analysis indicated immune dysfunction in BA, linked to altered immunoglobulin levels.
- A diagnostic model combining polymeric immunoglobulin receptor and immunoglobulin lambda variable chain achieved high accuracy (0.89) and AUC (0.944).
Conclusions:
- The study identified a promising plasma biomarker panel for the early diagnosis of biliary atresia.
- The findings contribute to understanding the immunological mechanisms underlying BA.
- This novel diagnostic approach has the potential to significantly improve early detection and management of BA in infants.
Abstract:
Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of pediatric patients with BA. Herein, we performed proteomics analysis using data-independent acquisition (DIA) and parallel reaction monitoring (PRM) to explore potential biomarkers for the early diagnosis of BA compared to other non-BA jaundice cases. Consequently, we detected and validated differential protein expression in the plasma of patients with BA compared to the plasma of patients with intrahepatic cholestasis. Bioinformatics analysis revealed the enriched biological processes characteristic of BA by identifying the differential expression of specific proteins. Signaling pathway analysis revealed changes in the expression levels of proteins associated with an alteration in immunoglobulin levels, which is indicative of immune dysfunction in BA. The combination of polymeric immunoglobulin receptor expression and immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), as revealed via machine learning, provided a useful early diagnostic model for BA, with a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and area under the curve value of 0.944. Thus, our study identified a possible effective plasma biomarker for the early diagnosis of BA and could help elucidate the underlying mechanisms of BA.
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