MFAP4 as a novel biomarker for predicting liver fibrosis and prognosis in infants with biliary atresia through the integration of bioinformatics with clinical data analysis.
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引用次数: 0
Abstract
Background: Biliary atresia (BA) is a progressive obliteration of intrahepatic and extrahepatic bile ducts. Our study aimed to identify and validate hub genes that are differentially expressed in BA, and to investigate their relationship with liver fibrosis.
Methods: The BA microarray datasets GSE46960 and GSE15235 were downloaded from the Gene Expression Omnibus (GEO) database. Clinical BA liver tissue samples were collected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB). Serum samples were analyzed for MFAP4 content using enzyme-linked immunosorbent assay (ELISA), and the corresponding clinical data of pediatric patients were collected. The relationship between serum MFAP4 levels and liver fibrosis, as well as prognosis, was investigated using ROC curve analysis. Furthermore, Kaplan-Meier (KM) curves were used to validate the prognostic significance of MFAP4 levels.
Results: Through bioinformatics analysis and experimental validation, MFAP4 was identified as a hub gene. MFAP4 via PCR and immunohistochemistry is significantly upregulated in biliary atresia compared to total functional cyst liver tissue. Serum MFAP4 levels accurately reflects the degree of liver fibrosis in patients with BA. High serum MFAP4 levels predicted a poorer native liver survival rate one year after Kasai surgery.
Conclusions: We discovered that MFAP4 is a crucial BA-associated gene, and validated its expression in BA. Furthermore, serum MFAP4 levels may serve as predictive markers for the degree of liver fibrosis and autologous liver survival after Kasai surgery.
背景：胆道闭锁（BA）是一种进行性肝内和肝外胆管阻塞。我们的研究旨在鉴定和验证BA中差异表达的枢纽基因，并探讨其与肝纤维化的关系。方法：从Gene Expression Omnibus （GEO）数据库下载BA微阵列数据集GSE46960和GSE15235。收集临床BA肝组织标本进行定量逆转录聚合酶链反应（qRT-PCR）和免疫印迹（WB）检测。采用酶联免疫吸附试验（ELISA）分析患儿血清中MFAP4的含量，并收集患儿相应的临床资料。采用ROC曲线分析血清MFAP4水平与肝纤维化及预后的关系。此外，采用Kaplan-Meier （KM）曲线验证MFAP4水平的预后意义。结果：通过生物信息学分析和实验验证，确定MFAP4为枢纽基因。与全功能囊肿肝组织相比，经PCR和免疫组化检测，MFAP4在胆道闭锁中显著上调。血清MFAP4水平能准确反映BA患者肝纤维化程度。高血清MFAP4水平预示Kasai手术一年后较差的原生肝脏存活率。结论：我们发现MFAP4是一个重要的BA相关基因，并证实了其在BA中的表达。此外，血清MFAP4水平可作为Kasai手术后肝纤维化程度和自体肝存活的预测指标。
期刊介绍：
Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.
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