Bile proteomics for discovery of biomarkers to differentiate between gallbladder polyp and gallstone

Abstract

Gallbladder polyps and gallstones, despite having distinct pathological mechanisms, present similar clinical features that challenge accurate diagnosis and timely intervention. This study aimed to identify potential diagnostic biomarkers for distinguishing between these conditions through a comprehensive proteomic analysis of bile juice. Bile samples from patients with gallbladder polyps, gallstones, and healthy controls were analyzed using nano-liquid chromatography-tandem mass spectrometry. A total of 167 proteins were identified in polyp samples and 118 in gallstone samples, with 99 proteins shared between the two groups. Comparative analysis revealed 14 proteins significantly upregulated and 15 downregulated in gallbladder polyp samples. Gene Ontology and KEGG pathway analyses revealed that upregulated proteins in polyps were primarily involved in oxidative stress and metabolic processes, while downregulated proteins were associated with extracellular matrix organization. Most notably, hemoglobin subunits HBA1 and HBB showed significant elevation in polyps, indicating enhanced oxygen transport and inflammation, while extracellular matrix proteins LUM and EZR showed reduced expression, suggesting compromised structural integrity. These findings underscore the potential of differentially expressed proteins in bile as diagnostic biomarkers, offering a promising avenue for early and accurate differentiation between gallbladder polyps and gallstones. © The Author(s) 2025.