Diagnostic and Prognostic Values of Bile Biomarkers for Malignant Biliary Stenosis

INTRODUCTION: Differentiating between malignant and benign biliary strictures remains a clinical challenge because current diagnostic tools have limited sensitivity. The detection of tumour-related biomarkers directly in bile, which is in close contact with the lesion, may enhance diagnostic accuracy. This study aimed at evaluating the diagnostic and prognostic values of biliary concentrations of VEGF, PDGF-AA, IGF and MMPs in patients with extrahepatic cholangiocarcinoma (CCA), pancreatic ductal adenocarcinoma (PDAC), or benign obstruction. METHODS: A total of 100 consecutive patients undergoing ERCP for obstructive jaundice were enrolled and categorised into benign (n = 48), CCA (n = 23) and PDAC (n = 29) groups. Bile samples collected during ERCP were analysed. The diagnostic and prognostic performance of several biomarkers was assessed and, when appropriate, their incremental diagnostic value was assessed in comparison with standard bile cytology. RESULTS: Biliary concentrations of VEGF, MMP-1, MMP-2, MMP-7 and MMP-9 were significantly higher in malignant cases than in benign cases. VEGF demonstrated the best diagnostic accuracy (AUROC 0.86, sensitivity 87%, specificity 81%). MMP-1 and MMP-7 also showed good diagnostic values (AUROCs 0.79 and 0.81 respectively). In the multivariate analysis, VEGF was independently associated with the diagnosis of malignancy and PDAC, whereas both VEGF and MMP-2 were independently associated with CCA diagnosis. Using a predefined cut-off, bile VEGF showed a higher sensitivity than bile cytology, and their combination markedly reduced false-negative results. Regarding prognosis, higher PDGF-AA levels were independently associated with better survival rates. CONCLUSION: Biliary VEGF is a strong independent biomarker for the diagnosis of malignant biliary obstruction, both in PDAC and CCA. MMP-2 was independently associated with CCA diagnosis. PDGF-AA is a promising prognostic biomarker for malignant biliary strictures. These findings support the clinical potential of bile-based biomarkers for improving the diagnosis and assessing the prognosis of malignant biliary strictures.