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.

中文翻译：

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蛋白质组学定义了胆道闭锁早期诊断的血浆生物标志物

胆道闭锁 (BA) 的早期诊断对于提高 BA 儿科患者的生存机会和保护肝功能至关重要。在此，我们使用数据独立采集（DIA）和平行反应监测（PRM）进行蛋白质组学分析，以探索与其他非 BA 黄疸病例相比用于早期诊断 BA 的潜在生物标志物。因此，我们检测并验证了 BA 患者血浆中与肝内胆汁淤积患者血浆中的差异蛋白表达。生物信息学分析通过识别特定蛋白质的差异表达揭示了BA丰富的生物过程特征。信号通路分析揭示了与免疫球蛋白水平变化相关的蛋白质表达水平的变化，这表明 BA 中存在免疫功能障碍。通过机器学习揭示的聚合免疫球蛋白受体表达和免疫球蛋白 lambda 可变链 (IGL c2225_light_IGLV1-47_IGLJ2) 的组合为 BA 提供了有用的早期诊断模型，灵敏度为 0.8，特异性为 1，准确性为 0.89，面积曲线值 0.944 下。因此，我们的研究发现了一种可能有效的血浆生物标志物，可用于 BA 的早期诊断，并有助于阐明 BA 的潜在机制。