Microbiome-based diagnostic biomarkers in pancreatic ductal adenocarcinoma: Current evidence and translational challenges (Review)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, as the majority of patients are diagnosed at an advanced disease stage. CA19-9, the biomarker most commonly used in clinical practice, lacks adequate sensitivity and specificity for early PDAC detection. Increasing evidence indicates that alterations in gut, oral and tumor-associated microbiota are associated with PDAC development and progression, supporting the potential diagnostic value of microbiome-based biomarkers in this disease. Multiple diagnostic models have been developed for PDAC using fecal, salivary or tissue-derived microbial profiles, and the combination of microbial signatures with CA19-9 or metabolomic markers has improved diagnostic performance in a number of cohorts. Despite these advancements, the clinical translation of microbiome-based models remains limited by methodological heterogeneity, patient-related variability, low levels of microbial biomass in pancreatic tissue and a lack of large-scale prospective validation. In addition, the majority of available evidence for microbiota-based alterations in PDAC is derived from retrospective case-control studies, and the reported diagnostic performance should therefore be interpreted cautiously. The present review summarizes current evidence on PDAC-associated microbial alterations and microbiome-based diagnostic models, and discusses the methodological, biological and regulatory challenges that must be addressed before microbiota-based approaches can be integrated into routine clinical practice.