Fecal microbiome signatures of pancreatic cancer patients

Fecal microbiome signatures of pancreatic cancer patients
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DOI:
10.1038/s41598-019-53041-4
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发表时间:
2019-11-14
期刊:
影响因子:
4.6
通讯作者:
Gophna, Uri
Gophna, Uri
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Half, Elizabeth;Keren, Nirit;Gophna, Uri

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胰腺癌(PC)是发达国家癌症相关死亡的主要原因,由于大多数患者在诊断时患有不治之症,因此开发早期检测的筛查方法具有高度优先性。由于其代谢的重要性,胰腺功能的改变可能会影响肠道微生物群的组成,从而可能产生PC的生物标志物。然而,如果这些生物标志物对疾病的晚期具有特异性,则它们的有用性可能是有限的,所述晚期可能涉及合并症,例如胆道梗阻或糖尿病。在这项研究中,我们分析了30例胰腺癌患者,6例癌前病变患者,13例健康受试者和16例非酒精性脂肪肝患者的粪便微生物群,使用细菌16S rRNA基因的扩增子测序。PC和对照组之间有14个细菌特征,其中几个与最近中国队列的发现相同。基于微生物群的随机森林模型分类PC和对照样品,AUC为82.5%。然而,受试者间的变异性很高,并且在患有癌前胰腺病变的患者中也仅观察到一小部分PC相关的微生物信号,这意味着基于微生物组的此类病变的早期检测将具有挑战性。
Pancreatic cancer (PC) is a leading cause of cancer-related death in developed countries, and since most patients have incurable disease at the time of diagnosis, developing a screening method for early detection is of high priority. Due to its metabolic importance, alterations in pancreatic functions may affect the composition of the gut microbiota, potentially yielding biomarkers for PC. However, the usefulness of these biomarkers may be limited if they are specific for advanced stages of disease, which may involve comorbidities such as biliary obstruction or diabetes. In this study we analyzed the fecal microbiota of 30 patients with pancreatic adenocarcinoma, 6 patients with pre-cancerous lesions, 13 healthy subjects and 16 with non-alcoholic fatty liver disease, using amplicon sequencing of the bacterial 16S rRNA gene. Fourteen bacterial features discriminated between PC and controls, and several were shared with findings from a recent Chinese cohort. A Random Forest model based on the microbiota classified PC and control samples with an AUC of 82.5%. However, inter-subject variability was high, and only a small part of the PC-associated microbial signals were also observed in patients with pre-cancerous pancreatic lesions, implying that microbiome-based early detection of such lesions will be challenging.