Bile metabolic fingerprints distinguish biliary tract cancer from benign biliary diseases

Shouzhi Yang; Jing Fu; Wenhao Qin; Ruimin Wang; Mingye Gu; Yida Huang; Wanshan Liu; Haiyang Su; Xiaoyu Xu; Wei Chen; Ayizekeranmu Yiming; Bing Hu; Lin Huang; Kun Qian; Hongyang Wang

doi:10.1097/HEP.0000000000000957

Bile metabolic fingerprints distinguish biliary tract cancer from benign biliary diseases

Hepatology. 2024 Jun 11. doi: 10.1097/HEP.0000000000000957. Online ahead of print.

Authors

Shouzhi Yang^{1

2

3}, Jing Fu⁴, Wenhao Qin⁵, Ruimin Wang^{1

2

3}, Mingye Gu⁶, Yida Huang^{1

2

3}, Wanshan Liu^{1

2

3}, Haiyang Su^{1

2

3}, Xiaoyu Xu^{1

2

3}, Wei Chen^{1

2

3}, Ayizekeranmu Yiming^{1

2

3}, Bing Hu⁵, Lin Huang^{1

2}, Kun Qian³, Hongyang Wang⁴

Affiliations

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.

PMID: 38861680
DOI: 10.1097/HEP.0000000000000957

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%.