Bile molecular landscape provides pathological insight and classifies signatures predictive of carcinoma of the gall bladder

Abstract

Carcinoma of the gall bladder (CAGB) has a poor prognosis. Molecular analysis of bile could classify indicators of CAGB. Bile samples (n = 87; training cohort) were screened for proteomics and metabolomics signatures of cancer detection. In bile, CAGB showed distinct proteomic (217 upregulated, 258 downregulated) and metabolomic phenotypes (111 upregulated, 505 downregulated, p 1.5, false discovery rate 0.5, p 90% (p 0.94. Validation of the top four metabolites—toluene, 5,6-DHET, creatine, and phenylacetaldehyde—in separate cohorts (n = 80; bile [T1] and paired plasma [T2]) showed accuracy (99%) and sensitivity/specificity (>98%) for CAGB detection. Tissue validation showed bile 5,6-DHET positively correlated with tissue PCNA (proliferation), and caspase-3 linked to cancer development (r2 >0.5, p < 0.05). In conclusion, the bile molecular landscape provides critical molecular understanding and outlines metabolomic indicator panels for early CAGB detection.

Keywords

• MT: Regular Issue
• proteomics
• metabolomic profile
• gallbladder
• carcinoma
• gallstone