CTHRC1 serves as an indicator in biliary atresia for evaluating the stage of liver fibrosis and predicting prognosis

IF 4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Digestive and Liver Disease Pub Date : 2025-02-01 DOI:10.1016/j.dld.2024.07.004

Zequan Ding , Ruyi Zhang , Wei Zhu, Yao Lu, Zhongxian Zhu, Hua Xie, Weibing Tang

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Abstract

Background

Liver fibrosis is a pathological feature of biliary atresia (BA). However, both histological fibrosis stage and existing biomarkers fail to predict prognosis at the time of hepatoportonterostomy (HPE).

Aims

To explore the role of collagen triple- helix repeat containing-1 (CTHRC1) in BA.

Methods

CTHRC1 expression levels were detected and its association with liver fibrosis stage was analyzed in patients with BA. Immunohistochemistry and immunofluorescent analyses were performed to detect the expression and localization of CTHRC1. Epithelial-mesenchymal transition (EMT) and proliferation were analyzed in cholangiocytes treated with recombinant human CTHRC1 protein. Survival analyses were performed to assess the prognostic value of CTHRC1 in patients with BA.

Results

CTHRC1 was upregulated in BA, and its expression level was positively correlated with fibrosis-related markers and the severity of liver fibrosis. In liver tissue CTHRC1 was co-localized with CK19 and highly expressed in patients with severe liver fibrosis. Further experiments revealed that CTHRC1 promoted cholangiocyte EMT and proliferation. Additionally, CTHRC1 expression levels at HPE could predict the 2-year native liver survival (NLS).

Conclusions

CTHRC1 promotes the EMT and proliferation of cholangiocytes and indicate the stage of liver fibrosis. The CTHRC1 expression levels can predict outcomes of BA.

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CTHRC1 是胆道闭锁患者评估肝纤维化阶段和预测预后的指标。

背景：肝纤维化是胆道闭锁（BA）的病理特征：肝纤维化是胆道闭锁（BA）的病理特征之一。然而，组织学纤维化分期和现有的生物标志物都无法预测肝门部造口术（HPE）时的预后：方法：检测 BA 患者中 CTHRC1 的表达水平，并分析其与肝纤维化分期的关系。免疫组化和免疫荧光分析检测了CTHRC1的表达和定位。分析了用重组人 CTHRC1 蛋白处理的胆管细胞的上皮-间质转化（EMT）和增殖情况。进行了生存分析，以评估CTHRC1在胆管癌患者中的预后价值：结果：CTHRC1在胆汁淤积症中上调，其表达水平与肝纤维化相关标志物和肝纤维化严重程度呈正相关。在肝组织中，CTHRC1与CK19共定位，并在严重肝纤维化患者中高表达。进一步的实验发现，CTHRC1 能促进胆管细胞的 EMT 和增殖。此外，CTHRC1在HPE中的表达水平可预测2年原肝存活率（NLS）：结论：CTHRC1能促进胆管细胞的EMT和增殖，并预示肝纤维化的阶段。结论：CTHRC1能促进胆管细胞的EMT和增殖，并预示肝纤维化的阶段，CTHRC1的表达水平能预测BA的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Digestive and Liver Disease 医学-胃肠肝病学

CiteScore

6.10

自引率

2.20%

发文量

632

审稿时长

19 days

期刊介绍： Digestive and Liver Disease is an international journal of Gastroenterology and Hepatology. It is the official journal of Italian Association for the Study of the Liver (AISF); Italian Association for the Study of the Pancreas (AISP); Italian Association for Digestive Endoscopy (SIED); Italian Association for Hospital Gastroenterologists and Digestive Endoscopists (AIGO); Italian Society of Gastroenterology (SIGE); Italian Society of Pediatric Gastroenterology and Hepatology (SIGENP) and Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Digestive and Liver Disease publishes papers on basic and clinical research in the field of gastroenterology and hepatology. Contributions consist of: Original Papers Correspondence to the Editor Editorials, Reviews and Special Articles Progress Reports Image of the Month Congress Proceedings Symposia and Mini-symposia.