MUC5AC in pancreatic cancer and precursors: a systematic review and meta-analysis

Abstract Background Mucin5AC (MUC5AC) is a secretory glycoprotein that is highly expressed in pancreatic cancer and precursors. We assessed its diagnostic accuracy in differentiating pancreatic cancer and precursors from normal pancreas and benign pancreatic diseases. Methods Systematic literature search was conducted through PubMed, Embase, Web of Science, and Google Scholar. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using a bivariate random effects model. Sources of heterogeneity, subgroup analysis, influence analysis, and publication bias assessment were conducted. Results We identified 55 studies including 2804 pancreatic cancer, 1088 precursors, 1048 benign diseases, and 1022 healthy controls. Tissue-based MUC5AC test showed a high diagnostic accuracy for differentiating pancreatic cancer from healthy controls (AUC = 0.94, 95% confidence interval [CI] 0.91–0.96, sensitivity = 0.70, 95% CI 0.57–0.81, specificity = 0.98, 95% CI 0.91-1.00) and from benign diseases (AUC = 0.94, 95% CI 0.91–0.96, sensitivity = 0.65, 95% CI 0.40–0.83, specificity = 0.89, 95% CI 0.75–0.95). Similarly, tissue-based MUC5AC differentiated precursors from heathy controls (AUC = 0.95, 95% CI 0.92–0.96, sensitivity = 0.79, 95% CI 0.65–0.89, specificity = 0.98, 95% CI 0.73-1.00) and benign diseases (sensitivity = 0.97, 95% CI 0.87 –0.99, specificity = 0.93, 95% CI 0.76–0.98). Tissue-based MUC5AC failed to differentiate pancreatic cancer from precursors (AUC = 0.29, 95% CI 0.25–0.33, sensitivity = 0.80, 95% CI 0.61–0.90, specificity = 0.08, 95% CI 0.04–0.17). Moreover, MUC5AC comparably differentiated early-stage and late-stage pancreatic cancer from benign diseases, with AUC = 0.82, 95% CI 0.78–0.85, sensitivity = 0.61, 95% CI 0.39–0.80, specificity = 0.85, 95% CI 0.70–0.93 and AUC = 0.82, 95% CI 0.79–0.85, sensitivity = 0.72, 95% CI 0.60–0.82, specificity = 0.87, 95% CI 0.74–0.94, respectively. Additionally, its expression in blood demonstrated a lower but moderate discriminative ability for pancreatic cancer from benign diseases (AUC = 0.83, 95% CI 0.80–0.86, sensitivity = 0.63, 95% CI 0.42–0.80, specificity = 0.91, 95% CI 0.78–0.96). Conclusions MUC5AC is a promising tissue biomarker for distinguishing pancreatic cancer or precursors from healthy pancreas or benign pancreatic diseases but not separating pancreatic cancer from its precursors. More studies are needed to reveal its role as a non-invasive diagnostic biomarker for pancreatic cancer or precursor lesions. Trial registration This study was registered in PROSPERO (ID: CRD42023495046).