Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
BGI-Shenzhen, Shenzhen, China.
Gut. 2017 Jan;66(1):70-78. doi: 10.1136/gutjnl-2015-309800. Epub 2015 Sep 25.
To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.
We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls.
Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC.
We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.
从粪便宏基因组评估诊断结直肠癌（CRC）的潜力。
我们在中国对 74 名 CRC 患者和 54 名对照的粪便样本进行了宏基因组关联研究，并在来自丹麦的 16 名患者和 24 名对照中验证了结果。我们还在法国和奥地利的两个已发表队列中验证了这些生物标志物。最后，我们采用靶向定量 PCR（qPCR）检测评估了在 47 名患者和 109 名对照的独立中国队列中选择的生物标志物的诊断潜力。
除了确认已知的具核梭杆菌和口腔普雷沃氏菌与 CRC 的关联外，我们还发现了与几种物种的显著关联，包括微小普雷沃氏菌和索氏梭杆菌。我们鉴定了 20 个区分 CRC 和对照微生物组的微生物基因标志物，并在丹麦队列中验证了 4 个标志物。在法国和奥地利队列中，这四个基因将 CRC 宏基因组与对照区分开来，ROC 曲线下面积（AUC）分别为 0.72 和 0.77。这些基因中两个的 qPCR 测量值准确地将中国独立队列中的 CRC 患者分类，AUC 为 0.84，OR 为 23。这些基因在早期（I-II 期）患者微生物组中富集，突出了使用粪便宏基因组生物标志物进行 CRC 早期诊断的潜力。
我们首次对 CRC 粪便微生物组进行了宏基因组分析研究，在不同种族的队列中发现并验证了微生物生物标志物，并使用负担得起的临床相关技术独立验证了选定的生物标志物。因此，我们的研究朝着从粪便样本中获得负担得起的非侵入性早期 CRC 诊断生物标志物又迈进了一步。
