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| Item Type: | Article |
|---|---|
| Title: | A faecal microbiota signature with high specificity for pancreatic cancer |
| Creators Name: | Kartal, E. and Schmidt, T.S.B. and Molina-Montes, E. and Rodríguez-Perales, S. and Wirbel, J. and Maistrenko, O.M. and Akanni, W.A. and Alashkar Alhamwe, B. and Alves, R.J. and Carrato, A. and Erasmus, H.P. and Estudillo, L. and Finkelmeier, F. and Fullam, A. and Glazek, A.M. and Gómez-Rubio, P. and Hercog, R. and Jung, F. and Kandels, S. and Kersting, S. and Langheinrich, M. and Márquez, M. and Molero, X. and Orakov, A. and Van Rossum, T. and Torres-Ruiz, R. and Telzerow, A. and Zych, K. and Benes, V. and Zeller, G. and Trebicka, J. and Real, F.X. and Malats, N. and Bork, P. |
| 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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