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口腔微生物群的变化与包括胰腺癌在内的胰腺疾病有关。

Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer.

机构信息

Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

出版信息

Gut. 2012 Apr;61(4):582-8. doi: 10.1136/gutjnl-2011-300784. Epub 2011 Oct 12.

DOI:10.1136/gutjnl-2011-300784
PMID:21994333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3705763/
Abstract

OBJECTIVE

The associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis.

METHODS

This study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples.

RESULTS

Comprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (Neisseria elongata and Streptococcus mitis) were validated using the independent samples, showing significant variation (p<0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (Granulicatella adiacens and S mitis) showed significant variation (p<0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (N elongata and S mitis) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p<0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects.

CONCLUSIONS

The authors observed associations between variations of patients' salivary microbiota with pancreatic cancer and chronic pancreatitis. This report also provides proof of salivary microbiota as an informative source for discovering non-invasive biomarkers of systemic diseases.

摘要

目的

几项前瞻性队列研究报告称,口腔疾病与胰腺癌风险增加之间存在关联。在这项研究中,我们测量了唾液微生物群的变化,并评估了它们与胰腺癌和慢性胰腺炎的潜在关联。

方法

这项研究分为三个阶段:(1)使用人类口腔微生物鉴定微阵列(Human Oral Microbe Identification Microarray)来研究 10 例可切除胰腺癌患者和 10 例匹配的健康对照者之间唾液微生物组的变化;(2)通过实时定量 PCR(qPCR)鉴定和验证细菌候选物;(3)在独立队列的 28 例可切除胰腺癌、28 例匹配的健康对照和 27 例慢性胰腺炎样本中通过 qPCR 验证细菌候选物。

结果

综合比较胰腺癌患者和健康对照者的唾液微生物群,发现唾液微生物群有明显的变化。与健康对照组(n=10)相比,胰腺癌患者(n=10)的唾液中有 31 种细菌物种/菌群增加,而 25 种细菌物种/菌群减少。在使用独立样本验证的 6 个细菌候选物中,有 2 个(Neisseria elongata 和 Streptococcus mitis)显示出显著差异(p<0.05,qPCR),其中包括胰腺癌患者和对照组(n=56)之间。此外,两种细菌(Granulicatella adiacens 和 S mitis)在慢性胰腺炎样本和对照组(n=55)之间也显示出显著差异(p<0.05,qPCR)。两种细菌生物标志物(N elongata 和 S mitis)的组合产生了 0.90(95%置信区间 0.78 至 0.96,p<0.0001)的受试者工作特征曲线下面积,其在区分胰腺癌患者和健康受试者方面具有 96.4%的灵敏度和 82.1%的特异性。

结论

作者观察到患者唾液微生物群的变化与胰腺癌和慢性胰腺炎之间存在关联。本报告还提供了唾液微生物群作为发现系统性疾病非侵入性生物标志物的信息来源的证据。

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