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A faecal microbiota signature with high specificity for pancreatic cancer

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Item Type:Article
Title:A faecal microbiota signature with high specificity for pancreatic cancer
Creators: Kartal, E. ORCID logoORCID: https://orcid.org/0000-0002-7720-455X, Schmidt, T.S.B. ORCID logoORCID: https://orcid.org/0000-0001-8587-4177, Molina-Montes, E. ORCID logoORCID: https://orcid.org/0000-0002-0428-2426, Rodríguez-Perales, S. ORCID logoORCID: https://orcid.org/0000-0001-7221-3636, Wirbel, J. ORCID logoORCID: https://orcid.org/0000-0002-4073-3562, Maistrenko, O.M. ORCID logoORCID: https://orcid.org/0000-0003-1961-7548, Akanni, W.A. ORCID logoORCID: https://orcid.org/0000-0002-2075-2387, Alashkar Alhamwe, B. ORCID logoORCID: https://orcid.org/0000-0002-7120-0013, Alves, R.J. ORCID logoORCID: https://orcid.org/0000-0002-7212-0234, Carrato, A. ORCID logoORCID: https://orcid.org/0000-0001-7749-8140, Erasmus, H.P., Estudillo, L. ORCID logoORCID: https://orcid.org/0000-0003-3891-3713, Finkelmeier, F., Fullam, A. ORCID logoORCID: https://orcid.org/0000-0002-0884-8124, Glazek, A.M., Gómez-Rubio, P., Hercog, R., Jung, F. ORCID logoORCID: https://orcid.org/0000-0002-5534-7832, Kandels, S. ORCID logoORCID: https://orcid.org/0000-0002-4194-4927, Kersting, S. ORCID logoORCID: https://orcid.org/0000-0002-2124-3103, Langheinrich, M. ORCID logoORCID: https://orcid.org/0000-0002-0120-9135, Márquez, M., Molero, X., Orakov, A. ORCID logoORCID: https://orcid.org/0000-0001-6823-5269, Van Rossum, T. ORCID logoORCID: https://orcid.org/0000-0002-3598-5001, Torres-Ruiz, R. ORCID logoORCID: https://orcid.org/0000-0001-9606-0398, Telzerow, A. ORCID logoORCID: https://orcid.org/0000-0001-9855-0809, Zych, K. ORCID logoORCID: https://orcid.org/0000-0001-7426-0516, Benes, V. ORCID logoORCID: https://orcid.org/0000-0002-0352-2547, Zeller, G. ORCID logoORCID: https://orcid.org/0000-0003-1429-7485, Trebicka, J. ORCID logoORCID: https://orcid.org/0000-0002-7028-3881, Real, F.X. ORCID logoORCID: https://orcid.org/0000-0001-9501-498X, Malats, N. ORCID logoORCID: https://orcid.org/0000-0003-2538-3784 and Bork, P. ORCID logoORCID: https://orcid.org/0000-0002-2627-833X
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.
Keywords:16S Ribosomal RNA, CA-19-9 Antigen, Case-Control Studies, Microbiota, Pancreatic Ductal Carcinoma, Pancreatic Neoplasms, Tumor Biomarkers
Source:Gut
ISSN:0017-5749
Publisher:BMJ Publishing Group
Volume:71
Number:7
Page Range:1359-1372
Date:7 June 2022
Official Publication:https://doi.org/10.1136/gutjnl-2021-324755
PubMed:View item in PubMed

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