A faecal microbiota signature with high specificity for pancreatic cancer

Kartal E, Schmidt TSB, Molina-Montes E, Rodriguez-Perales S, Wirbel J, Maistrenko OM, Akanni WA, Alhamwe BA, Alves RJ, Carrato A, Erasmus HP, Estudillo L, Finkelmeier F, Fullam A, Glazek AM, Gomez-Rubio P, Hercog R, Jung F, Kandels S, Kersting S, Langheinrich M, Marquez M, Molero X, Orakov A, Van Rossum T, Torres-Ruiz R, Telzerow A, Zych K, Benes V, Zeller G, Trebicka J, Real FX, Malats N, Bork P (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Gut BMJ Publishing Group

DOI: 10.1136/gutjnl-2021-324755

Abstract

Background Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) aetiology and progression. 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.

Involved external institutions

European Molecular Biology Laboratory (EMBL) DE Germany (DE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) ES Spain (ES) Universität Greifswald DE Germany (DE) Goethe-Universität Frankfurt am Main DE Germany (DE) Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) ES Spain (ES) Philipps-Universität Marburg DE Germany (DE) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES)

How to cite

APA:

Kartal, E., Schmidt, T.S.B., Molina-Montes, E., Rodriguez-Perales, S., Wirbel, J., Maistrenko, O.M.,... Bork, P. (2022). A faecal microbiota signature with high specificity for pancreatic cancer. Gut. https://doi.org/10.1136/gutjnl-2021-324755

MLA:

Kartal, Ece, et al. "A faecal microbiota signature with high specificity for pancreatic cancer." Gut (2022).

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