Metagenomic Microbial Signatures for Noninvasive Detection of Pancreatic Cancer

<b>Background/Objectives:</b> Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor early detection rates owing to the limited sensitivity and specificity of the current biomarker CA19-9. Gut microbiota dysbiosis plays a key role in PDAC pathogenesis. This study aimed to evaluate the noninvasive approach we developed, combining metagenome-derived microbial signatures with CA19-9, to improve PDAC detection. <b>Methods:</b> This study included 50 treatment-naïve patients with PDAC and their matched controls. Fecal samples were analyzed using shotgun metagenomic sequencing. Machine learning algorithms were used to develop and validate a diagnostic panel integrating microbial signatures and CA19-9 levels. Subgroup analyses were used to confirm the robustness of the microbial markers. <b>Results:</b> The combined models at both species and genus levels effectively distinguished patients with PDAC from healthy individuals, and their strong diagnostic efficacy and accuracy were demonstrated through rigorous validation. <b>Conclusions:</b> In conclusion, the combination of gut microbiome profiling and CA19-9 improves PDAC detection accuracy compared to the use of CA19-9 alone, showing promise for early and noninvasive diagnosis.