A faecal microbiota signature with high specificity for pancreatic cancer.
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Kartal Ece, Schmidt Thomas S B, Molina-Montes Esther, Rodríguez-Perales Sandra, Wirbel Jakob, Maistrenko Oleksandr M, Akanni Wasiu A, Alashkar Alhamwe Bilal, Alves Renato J, Carrato Alfredo, Erasmus Hans-Peter, Estudillo Lidia, Finkelmeier Fabian, Fullam Anthony, Glazek Anna M, Gómez-Rubio Paulina, Hercog Rajna, Jung Ferris, Kandels Stefanie, Kersting Stephan, Langheinrich Melanie, Márquez Mirari, Molero Xavier, Orakov Askarbek, Van Rossum Thea, Torres-Ruiz Raul, Telzerow Anja, Zych Konrad, MAGIC Study investigators, PanGenEU Study investigators, Benes Vladimir, Zeller Georg, Trebicka Jonel, Real Francisco X, Malats Nuria, Bork Peer
Аннотация
OBJECTIVE: To explore the faecal and salivary microbiota as potential diagnostic biomarkers.
METHODS: We applied shotgun metagenomic and 16S rRNA amplicon sequencing to samples from a Spanish case-control study (n=136), including 57 cases, 50 controls, and 29 patients with chronic pancreatitis in the discovery phase, and from a German case-control study (n=76), in the validation phase.
RESULTS: Faecal metagenomic classifiers performed much better than saliva-based classifiers and identified patients with PDAC with an accuracy of up to 0.84 area under the receiver operating characteristic curve (AUROC) based on a set of 27 microbial species, with consistent accuracy across early and late disease stages. Performance further improved to up to 0.94 AUROC when we combined our microbiome-based predictions with serum levels of carbohydrate antigen (CA) 19-9, the only current non-invasive, Food and Drug Administration approved, low specificity PDAC diagnostic biomarker. Furthermore, a microbiota-based classification model confined to PDAC-enriched species was highly disease-specific when validated against 25 publicly available metagenomic study populations for various health conditions (n=5792). Both microbiome-based models had a high prediction accuracy on a German validation population (n=76). Several faecal PDAC marker species were detectable in pancreatic tumour and non-tumour tissue using 16S rRNA sequencing and fluorescence in situ hybridisation.
CONCLUSION: Taken together, our results indicate that non-invasive, robust and specific faecal microbiota-based screening for the early detection of PDAC is feasible.