Key Mucins in Early Diagnosis of Pancreatic Ductal Adenocarcinoma and Biliary Tract Cancer: A Meta-Analysis

The aim of the study was to evaluate the diagnostic accuracy of mucins in pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) based on available evidence and to assess their role in differential diagnosis. A comprehensive search was conducted across PubMed/MEDLINE, Web of Science, Embase and Cochrane Library from database inception to September 2024. All immunoassay-based cases or clinical studies that investigated mucin (MUC) in relation to PDAC or BTC were included. The pooled sensitivity and specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), the area under the summary receiver operating characteristic (SROC) curve, and the area under the curve (AUC) for several mucins in diagnosing PDAC and BTC were assessed. A total of 56 studies involving 6823 patients were included in the analysis. Current mucin-based diagnostic approaches for PDAC and BTC primarily focus on mucin 1 (MUC1), mucin 2 (MUC2), mucin 4 (MUC4), mucin 5AC (MUC5AC), and mucin 6 (MUC6). Among them, MUC1 demonstrated exceptional diagnostic performance in PDAC with a sensitivity of 0.96 and a specificity of 0.76 and in BTC with a sensitivity of 0.80 and a specificity of 0.93. Additionally, MUC4 also exhibited good diagnostic efficacy in PDAC, with a sensitivity of 0.77 and a specificity of 0.76. MUC5AC demonstrated significant diagnostic efficacy in PDAC with a sensitivity of 0.79 and a specificity of 0.61 and in BTC with a sensitivity of 0.69 and a specificity of 0.77. However, the other two proteins, MUC2 and MUC6, exhibited poor diagnostic performance for PDAC and BTC, with a sensitivities of less than 0.47 and a specificities of less than 0.68. In conclusion, this meta-analysis of patients with PDAC and BTC indicates that MUC markers may have high diagnostic accuracy, particularly some specific key mucins. The differential expression of the same mucin in both cancers as well as in their corresponding benign diseases offers valuable insights into the differential diagnosis.