Bile metabolic fingerprints distinguish biliary tract cancer from benign biliary diseases-Reference-Cited by-同舟云学术

Bile metabolic fingerprints distinguish biliary tract cancer from benign biliary diseases

Published:2024-06-11 Issue: Volume: Page:
ISSN:0270-9139
Container-title:Hepatology
language:en
Short-container-title:

Author:

Yang Shouzhi¹²³^ORCID,Fu Jing⁴,Qin Wenhao⁵,Wang Ruimin¹²³^ORCID,Gu Mingye⁶,Huang Yida¹²³^ORCID,Liu Wanshan¹²³^ORCID,Su Haiyang¹²³,Xu Xiaoyu¹²³,Chen Wei¹²³,Yiming Ayizekeranmu¹²³,Hu Bing⁵,Huang Lin¹²^ORCID,Qian Kun³^ORCID,Wang Hongyang⁴^ORCID

Affiliation:

1. Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

2. Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

3. State Key Laboratory of Systems Medicine for Cancer, School of Biomedical Engineering, Institute of Medical Robotics and Shanghai Academy of Experimental Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

4. International Cooperation Laboratory on Signal Transduction, National Center for Liver Cancer, Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai, P.R. China

5. Department of Gastroenterology and Endoscopy, Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai, P.R. China

6. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

Abstract

Background and Aims: Biliary tract cancers are aggressive gastrointestinal malignancies characterized by a dismal 5-year overall survival rate <20%. Current diagnostic modalities suffer from limitations regarding sensitivity and specificity. This study aimed to develop a bile metabolite–based platform for precise discrimination between malignant and benign biliary diseases. Approach and Results: Samples were collected from 336 patients with biliary tract cancer or benign biliary diseases across 3 independent cohorts. Untargeted metabolic fingerprinting was performed on 300 bile samples using novel nanoparticle-enhanced laser desorption/ionization mass spectrometry. Subsequently, a diagnostic assay was developed based on the exploratory cohort using a selected bile metabolic biomarker panel, with performance evaluated in the validation cohort. Further external validation of disease-specific metabolites from bile samples was conducted in a prospective cohort (n = 36) using quantitative analysis. As a result, we established a novel bile-based assay, BileMet, for the rapid and precise detection of malignancies in the biliary tract system with an AUC of 0.891. We identified 6-metabolite biomarker candidates and discovered the critical role of the chenodeoxycholic acid glycine conjugate as a protective metabolite associated with biliary tract cancer. Conclusions: Our findings confirmed the improved diagnostic capabilities of BileMet assay in a clinical setting. If applied, the BileMet assay enables intraoperative testing and fast medical decision-making for cases with suspected malignancy where brush cytology detection fails to support malignancy, ultimately reducing the economic burden by over 90%.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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