A faecal microbiota signature with high specificity for pancreatic cancer.
A faecal microbiota signature with high specificity for pancreatic cancer.
复制标题
对胰腺癌具有高度特异性的粪便微生物群特征。
DOI：
10.1136/gutjnl-2021-324755
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发表时间：
2022-07
期刊：
影响因子：
24.5
通讯作者：
Bork, Peer
中科院分区：
文献类型：
--
作者：
Kartal, Ece;Schmidt, Thomas S. B.;Molina-Montes, Esther;Rodriguez-Perales, Sandra;Wirbel, Jakob;Maistrenko, Oleksandr M.;Akanni, Wasiu A.;Alhamwe, Bilal Alashkar;Alves, Renato J.;Carrato, Alfredo;Erasmus, Hans-Peter;Estudillo, Lidia;Finkelmeier, Fabian;Fullam, Anthony;Glazek, Anna M.;Gomez-Rubio, Paulina;Hercog, Rajna;Jung, Ferris;Kandels, Stefanie;Kersting, Stephan;Langheinrich, Melanie;Marquez, Mirari;Molero, Xavier;Orakov, Askarbek;Van Rossum, Thea;Torres-Ruiz, Raul;Telzerow, Anja;Zych, Konrad;Benes, Vladimir;Zeller, Georg;Trebicka, Jonel;Real, Francisco X.;Malats, Nuria;Bork, Peer
最近的证据表明微生物组在胰腺导管腺癌（PDAC）病因和进展中的作用。探索粪便和唾液微生物群作为潜在的诊断生物标志物。我们应用鸟枪宏基因组和16 S rRNA扩增子测序的样本来自西班牙病例对照研究（n=136），包括57例病例，50例对照和29例慢性胰腺炎患者在发现阶段，并从德国病例对照研究（n=76），在验证阶段。粪便宏基因组分类器比基于唾液的分类器表现得更好，并且基于一组27种微生物物种以高达0.84的受试者工作特征曲线（AUROC）下面积的准确度识别PDAC患者，在早期和晚期疾病阶段具有一致的准确度。当我们将基于微生物组的预测与碳水化合物抗原（CA）19-9的血清水平相结合时，性能进一步提高至0.94 AUROC，CA 19-9是目前唯一一种非侵入性的、食品和药物管理局批准的低特异性PDAC诊断生物标志物。此外，基于微生物的分类模型局限于PDAC富集的物种是高度疾病特异性验证时，对25个公开的宏基因组研究人群的各种健康状况（n=5792）。这两种基于微生物组的模型对德国验证人群（n=76）的预测准确度很高。使用16 S rRNA测序和荧光原位杂交，在胰腺肿瘤和非肿瘤组织中可检测到几种粪便PDAC标记物。综上所述，我们的研究结果表明，非侵入性的，强大的和具体的粪便微生物为基础的筛选早期检测PDAC是可行的。
Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) aetiology and progression. To explore the faecal and salivary microbiota as potential diagnostic biomarkers. 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. 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. Taken together, our results indicate that non-invasive, robust and specific faecal microbiota-based screening for the early detection of PDAC is feasible.
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