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

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

  • Med. 2025 Sep 2:100843. doi: 10.1016/j.medj.2025.100843.
Long Gao 1,  Baoquan Xiao 2,  Yanyan Lin 1,  Xidong Fang 3,  Shun He 4,  Mingzhen Bai 1,  Lingen Zhang 1,  Yanni Ma 1,  Ningning Mi 1,  Wenkang Fu 1,  Chongfei Huang 1,  Liang Tian 1,  Jinyu Zhao 1,  Ruyang Zhong 1,  Zhen Liu 1,  Yanxian Ren 1,  Chao Zhang 4,  Ruoshui Wang 4,  Chenjun Tian 4,  Hui Sun 5,  Emmanuel Melloul 6,  Qiangqiang Zhang 7,  Jinqiu Yuan 8,  Ping Yue 9,  Liyun Ding 10,  Wenbo Meng 11
Affiliations

Affiliations

  • 1 Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
  • 2 School of Physical Science and Technology, Lanzhou University, Lanzhou, Gansu 730030, China.
  • 3 The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730030, China.
  • 4 Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 5 Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China.
  • 6 Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
  • 7 Key Laboratory of Mechanics on Disaster and Environment in Western China, Lanzhou University, Lanzhou, Gansu 730030, China.
  • 8 Clinical Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China. Electronic address: yuanjq5@mail.sysu.edu.cn.
  • 9 Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, China. Electronic address: ldyy_yuep@lzu.edu.cn.
  • 10 School of Physical Science and Technology, Lanzhou University, Lanzhou, Gansu 730030, China. Electronic address: dingly@lzu.edu.cn.
  • 11 Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, China; Gansu Province Key Laboratory of Biological Therapy and Regenerative Medicine Transformation, Lanzhou, Gansu 730030, China. Electronic address: mengwb@lzu.edu.cn.
PMID: 40930098 DOI: 10.1016/j.medj.2025.100843
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 KD 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.

Keywords

CLU; Translation to patients; cholangiocarcinoma; diagnosis; digestive endoscopy; optic fiber biosensor.

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