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具核梭杆菌与结直肠癌发生发展阶段、结直肠癌及疾病转归相关。

Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome.

作者信息

Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, Bruha J, Neary P, Dezeeuw N, Tommasino M, Jenab M, Prehn J H M, Hughes D J

机构信息

Centre for Systems Medicine and Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland.

出版信息

Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1381-90. doi: 10.1007/s10096-014-2081-3. Epub 2014 Mar 6.

Abstract

Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.

摘要

结肠中的共生细菌可能在结直肠癌(CRC)的发生发展中发挥作用。北美最近的研究表明,与CRC患者匹配的正常组织相比,具核梭杆菌(Fn)感染在疾病组织中更为常见。通过对来自三个欧洲队列共122例CRC患者的结直肠组织活检和手术切除样本中提取的DNA进行定量实时聚合酶链反应(qPCR),我们发现与匹配的正常组织相比,癌组织中Fn含量过高(p < 0.0001)。为了确定Fn感染是否是CRC发生发展的早期事件,我们检测了52例爱尔兰患者的结肠腺瘤(CRA)组织中的Fn。虽然所有CRA患者中,疾病组织中的Fn水平与正常组织相比在统计学上没有显著升高(p = 0.06),但在高级别发育异常中Fn水平显著升高(p = 0.015)。作为次要目标,我们确定Fn水平低的CRC患者的总生存时间明显长于Fn水平中等和高的患者(p = 0.008)。对Fn作为CRC筛查潜在非侵入性生物标志物的研究表明,虽然与腺瘤或对照组相比,CRC患者粪便样本中的Fn含量更高,但粪便中的水平与同一患者的癌症或腺瘤组织水平无关。这是第一项研究欧洲CRC和CRA患者结肠组织和粪便中Fn的研究,并表明Fn是腺瘤向癌症疾病进展的新危险因素,可能影响患者生存结果。我们的结果突出了检测Fn作为CRC患者诊断和预后决定因素的潜力。

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