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