• Long Gao, Yanyan Lin, Ping Yue, Shuyan Li, Yong Zhang, Ningning Mi, Mingzhen Bai, Wenkang Fu, Zhili Xia, Ningzu Jiang, Jie Cao, Man Yang, Yanni Ma, Fanxiang Zhang, Chao Zhang, Joseph W Leung, Shun He, Jinqiu Yuan, Wenbo Meng, and Xun Li.
• The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China.
• Bmc Med. 2023 Aug 8; 21 (1): 294294.

BackgroundCholangiocarcinoma (CCA) is a highly aggressive malignant tumor, and its diagnosis is still a challenge. This study aimed to identify a novel bile marker for CCA diagnosis based on proteomics and establish a diagnostic model with deep learning.MethodsA total of 644 subjects (236 CCA and 408 non-CCA) from two independent centers were divided into discovery, cross-validation, and external validation sets for the study. Candidate bile markers were identified by three proteomics data and validated on 635 clinical humoral specimens and 121 tissue specimens. A diagnostic multi-analyte model containing bile and serum biomarkers was established in cross-validation set by deep learning and validated in an independent external cohort.ResultsThe results of proteomics analysis and clinical specimen verification showed that bile clusterin (CLU) was significantly higher in CCA body fluids. Based on 376 subjects in the cross-validation set, ROC analysis indicated that bile CLU had a satisfactory diagnostic power (AUC: 0.852, sensitivity: 73.6%, specificity: 90.1%). Building on bile CLU and 63 serum markers, deep learning established a diagnostic model incorporating seven factors (CLU, CA19-9, IBIL, GGT, LDL-C, TG, and TBA), which showed a high diagnostic utility (AUC: 0.947, sensitivity: 90.3%, specificity: 84.9%). External validation in an independent cohort (n = 259) resulted in a similar accuracy for the detection of CCA. Finally, for the convenience of operation, a user-friendly prediction platform was built online for CCA.ConclusionsThis is the largest and most comprehensive study combining bile and serum biomarkers to differentiate CCA. This diagnostic model may potentially be used to detect CCA.© 2023. BioMed Central Ltd., part of Springer Nature.

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