粪便共生梭状芽孢杆菌用于非侵入性检测早期和晚期结直肠癌：检测和验证研究。

Fecal Clostridium symbiosum for Noninvasive Detection of Early and Advanced Colorectal Cancer: Test and Validation Studies.

机构信息

Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, 145 Middle Shandong Road, Shanghai 200001, China.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

出版信息

EBioMedicine. 2017 Nov;25:32-40. doi: 10.1016/j.ebiom.2017.10.005. Epub 2017 Oct 4.

DOI:10.1016/j.ebiom.2017.10.005

PMID:29033369

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5704049/

Abstract

OBJECTIVE

Current non-invasive early detection of colorectal cancer (CRC) requires improvement. We aimed to identified a fecal Clostridium symbiosum-based biomarker for early and advanced colorectal cancer detection.

DESIGN

In the test stage, the relative abundance of Clostridium symbiosum (C. symbiosum) was measured by qPCR in 781 cases including 242 controls, 212 colorectal adenoma (CRA) patients, 109 early CRC (tumor restricted to the submucosa) patients, 218 advanced CRC patients. The prediction accuracy was compared to Fusobacterium nucleatum (F. nucleatum), fecal immunochemical test (FIT) and CEA (carcinoembryonic antigen) and validated in an independent cohort of 256 subjects. Current status of the trial:ongoing/still enrolling. Primary endpoint:June, 2017 (Clinicaltrials.gov Identifier NCT02845973).

RESULTS

Significant stepwise increase of C. symbiosum abundance was found in CRA, early CRC and advanced CRC (P<0.01). C. symbiosum outperformed all the other markers in early CRC prediction performance. The combination of C. symbiosum and FIT achieved better performance (0.803 for test cohort and 0.707 for validation cohort). For overall discrimination of CRCs, the combination of all above markers achieved the performance of 0.876.

CONCLUSIONS

Fecal C. symbiosum is a promising biomarker for early and noninvasive detection of colorectal cancer, being more effective than F. nucleatum, FIT and CEA. Combining C. symbiosum and FIT or CEA may improve the diagnosis power.

摘要

目的

目前，对结直肠癌（CRC）的非侵入性早期检测需要改进。我们旨在确定一种基于粪便共生梭状芽孢杆菌的生物标志物，用于早期和晚期结直肠癌的检测。

设计

在测试阶段，通过 qPCR 测量了 781 例患者（包括 242 例对照、212 例结直肠腺瘤（CRA）患者、109 例早期 CRC（肿瘤局限于黏膜下层）患者和 218 例晚期 CRC 患者）中共生梭状芽孢杆菌（C. symbiosum）的相对丰度。将预测准确性与具核梭杆菌（F. nucleatum）、粪便免疫化学试验（FIT）和癌胚抗原（CEA）进行比较，并在 256 例独立队列中进行验证。试验现状：正在进行/仍在招募中。主要终点：2017 年 6 月（Clinicaltrials.gov 标识符：NCT02845973）。

结果

在 CRA、早期 CRC 和晚期 CRC 中发现共生梭状芽孢杆菌丰度呈显著逐步增加（P<0.01）。与其他所有标志物相比，共生梭状芽孢杆菌在早期 CRC 预测性能方面表现更好。共生梭状芽孢杆菌和 FIT 的组合具有更好的性能（测试队列为 0.803，验证队列为 0.707）。对于 CRC 的整体鉴别，上述所有标志物的组合达到了 0.876 的性能。