Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin.

IF 11.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-09-02 DOI:10.1016/j.medj.2025.100843

Long Gao, Baoquan Xiao, Yanyan Lin, Xidong Fang, Shun He, Mingzhen Bai, Lingen Zhang, Yanni Ma, Ningning Mi, Wenkang Fu, Chongfei Huang, Liang Tian, Jinyu Zhao, Ruyang Zhong, Zhen Liu, Yanxian Ren, Chao Zhang, Ruoshui Wang, Chenjun Tian, Hui Sun, Emmanuel Melloul, Qiangqiang Zhang, Jinqiu Yuan, Ping Yue, Liyun Ding, Wenbo Meng

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引用次数: 0

Abstract

Background: Early diagnosis of cholangiocarcinoma (CCA) remains challenging, but liquid biopsy is emerging as a promising detection strategy. Here, we identified a novel bile biomarker for CCA and developed an optic fiber biosensor integrated with digestive endoscopy for real-time diagnosis in vivo.

Methods: A total of 583 subjects and two proteomic analyses were used to screen and validate biomarkers for CCA, and then the corresponding antibodies were generated to construct a surface plasmon resonance (SPR)-based optic fiber biosensor. The diagnostic performance of the biosensor was validated in 120 patients in vitro, and its biological characteristics were assessed under various physiological conditions. Finally, its real-time detection and biosafety in vivo were verified in pigs and patients.

Findings: Clusterin (CLU) has been identified as a promising biomarker for CCA. Anti-CLU antibodies can specifically bind antigens with a K_D value of 0.231 nM, and the diameter of the antibody-coated biosensor is only 0.488 mm. The optic fiber biosensor can accurately detect different concentrations of CLU with an R² value of 0.989, and it cannot be disturbed by other free proteins, ions, or different temperatures, pH levels, and colors. The biosensor can identify CCA within 2 s with an area under curve (AUC) of 0.854. Moreover, the biosensor can be easily introduced into porcine bile ducts via digestive endoscopy with excellent biocompatibility. Then, the biosensor was applied to three patients with non-calculous biliary strictures, and the results of real-time detection matched postoperative pathology.

Conclusions: The CLU-based biosensor-endoscopy system enables accurate diagnosis of CCA through real-time in vivo detection, offering significant clinical translational potential.

Funding: Funding information is shown in the acknowledgments.

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基于胆管聚集素的消化内镜与光纤生物传感器联合实时诊断胆管癌。

背景：胆管癌（CCA）的早期诊断仍然具有挑战性，但液体活检正在成为一种有前途的检测策略。在这里，我们确定了一种新的胆汁生物标志物，并开发了一种集成了消化内窥镜的光纤生物传感器，用于体内实时诊断。方法：通过583名受试者和2项蛋白质组学分析，筛选并验证CCA生物标志物，生成相应抗体，构建基于表面等离子体共振（SPR）的光纤生物传感器。在120例患者体内验证了该生物传感器的诊断性能，并在各种生理条件下评估了其生物学特性。最后，在猪和患者身上验证了其实时检测和生物安全性。研究结果：聚簇素（CLU）已被确定为一种有前景的CCA生物标志物。Anti-CLU抗体能特异性结合KD值为0.231 nM的抗原，抗体包被的生物传感器直径仅为0.488 mm。光纤生物传感器能准确检测不同浓度的CLU， R2值为0.989，且不受其他游离蛋白、离子、不同温度、pH值、颜色的干扰。该传感器可在2 s内识别出CCA，曲线下面积（AUC）为0.854。该传感器具有良好的生物相容性，易于通过消化内窥镜植入猪胆管。将生物传感器应用于3例非结石性胆道狭窄患者，实时检测结果与术后病理吻合。结论：基于clu的生物传感器内窥镜系统能够通过实时体内检测准确诊断CCA，具有重要的临床转化潜力。资助：资助信息显示在致谢中。

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

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.