Microbiome Markers of Pancreatic Cancer Based on Bacteria-Derived Extracellular Vesicles Acquired from Blood Samples: A Retrospective Propensity Score Matching Analysis

SIMPLE SUMMARY: Although tremendous advances in diagnosis and treatment, pancreatic cancer still remains one of the lethal diseases with an overall survival rate of 10~15%. Early detection and diagnosis of pancreatic cancer is very important in improving the prognosis of patients. The aim of our study was to find new biomarkers, using microbiomes based on bacteria-derived extracellular vesicles, extracted from blood serum. With 38 patients with pancreatic cancer and 52 healthy controls with no history of pancreatic disease, we identified several compositional differences of microbiome between them. Using various combinations of the metagenomic markers which made the compositional differences, we also built a pancreatic cancer prediction model with high area under the receiver operating characteristic curve (0.966 at the phylum level and 1.000 at the genus level). These microbiome markers, based on bacteria-derived extracellular vesicles acquired from blood, show demonstrate the potential of candidate biomarkers for early diagnosis of pancreatic cancer. ABSTRACT: Novel biomarkers for early diagnosis of pancreatic cancer (PC) are necessary to improve prognosis. We aimed to discover candidate biomarkers by identifying compositional differences of microbiome between patients with PC (n = 38) and healthy controls (n = 52), using microbial extracellular vesicles (EVs) acquired from blood samples. Composition analysis was performed using 16S rRNA gene analysis and bacteria-derived EVs. Statistically significant differences in microbial compositions were used to construct PC prediction models after propensity score matching analysis to reduce other possible biases. Between-group differences in microbial compositions were identified at the phylum and genus levels. At the phylum level, three species (Verrucomicrobia, Deferribacteres, and Bacteroidetes) were more abundant and one species (Actinobacteria) was less abundant in PC patients. At the genus level, four species (Stenotrophomonas, Sphingomonas, Propionibacterium, and Corynebacterium) were less abundant and six species (Ruminococcaceae UCG-014, Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, Ruminiclostridium, and Lachnospiraceae UCG-001) were more abundant in PC patients. Using the best combination of these microbiome markers, we constructed a PC prediction model that yielded a high area under the receiver operating characteristic curve (0.966 and 1.000, at the phylum and genus level, respectively). These microbiome markers, which altered microbial compositions, are therefore candidate biomarkers for early diagnosis of PC.