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