Core Viewpoint - The study presents a novel method for real-time diagnosis of cholangiocarcinoma (CCA) by combining optical fiber biosensors based on bile clusterin with digestive endoscopy, addressing the urgent need for improved diagnostic techniques for this aggressive cancer type [2][10]. Summary by Sections Diagnosis Challenges - Cholangiocarcinoma is a highly malignant tumor with a poor prognosis, characterized by late diagnosis due to non-specific early symptoms, resulting in a 5-year survival rate of only 7%-20% [2]. Research Findings - The research team identified clusterin (CLU) as a promising biomarker for CCA through proteomic analysis of bile and cell supernatants, highlighting its overexpression in various cancers [5]. - The optical fiber biosensor technology, particularly surface plasmon resonance (SPR), was utilized for its high sensitivity and stability in detecting biological markers [5]. Methodology - The study involved 583 subjects and two rounds of proteomic analysis to screen and validate biomarkers for CCA, leading to the development of an SPR-based optical fiber biosensor [6]. - The biosensor demonstrated a high correlation coefficient of 0.989 and could accurately detect varying concentrations of CLU, with a detection time of 2 seconds and an area under the curve (AUC) of 0.854 [7]. Clinical Application - The CLU optical fiber biosensor was successfully integrated with digestive endoscopy, allowing for real-time in vivo diagnosis of CCA, with results aligning with postoperative pathology findings in patients [8][10].