Clinical Trial

. 2017 Nov:25:32-40.

doi: 10.1016/j.ebiom.2017.10.005. Epub 2017 Oct 4.

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

Yuan-Hong Xie¹, Qin-Yan Gao¹, Guo-Xiang Cai², Xiao-Min Sun, Xiao-Ming Sun^#³, Tian-Hui Zou¹, Hui-Min Chen¹, Si-Yi Yu¹, Yi-Wen Qiu¹, Wei-Qi Gu¹, Xiao-Yu Chen¹, Yun Cui¹, Danfeng Sun¹, Zhan-Ju Liu³, San-Jun Cai⁴, Jie Xu⁵, Ying-Xuan Chen⁶, Jing-Yuan Fang⁷

Affiliations

¹ 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.
² Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
³ Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
⁴ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address: csj@shca.org.cn.
⁵ 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. Electronic address: jiexu@sjtu.edu.cn.
⁶ 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. Electronic address: yingxuanchen71@sjtu.edu.cn.
⁷ 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. Electronic address: jingyuanfang@sjtu.edu.cn.

^# Contributed equally.

PMID: 29033369
PMCID: PMC5704049
DOI: 10.1016/j.ebiom.2017.10.005

Clinical Trial

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

Yuan-Hong Xie et al. EBioMedicine. 2017 Nov.

. 2017 Nov:25:32-40.

doi: 10.1016/j.ebiom.2017.10.005. Epub 2017 Oct 4.

Authors

Affiliations

¹ 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.
² Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
³ Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
⁴ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address: csj@shca.org.cn.
⁵ 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. Electronic address: jiexu@sjtu.edu.cn.
⁶ 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. Electronic address: yingxuanchen71@sjtu.edu.cn.
⁷ 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. Electronic address: jingyuanfang@sjtu.edu.cn.

^# Contributed equally.

PMID: 29033369
PMCID: PMC5704049
DOI: 10.1016/j.ebiom.2017.10.005

Erratum in

Corrigendum to "Fecal Clostridium Symbiosum for Noninvasive Detection of Early and Advanced Colorectal Cancer: Test and Validation Studies" [Ebiomedicine 25 (2017) 32-40].
Xie YH, Gao QY, Cai GX, Sun XM, Zou TH, Chen HM, Yu SY, Qiu YW, Gu WQ, Chen XY, Cui Y, Sun D, Liu ZJ, Cai SJ, Xu J, Chen YX, Fang JY. Xie YH, et al. EBioMedicine. 2018 May;31:320. doi: 10.1016/j.ebiom.2018.02.014. Epub 2018 Feb 20. EBioMedicine. 2018. PMID: 29691141 Free PMC article. No abstract available.

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.

Keywords: Clostridium symbiosum; Colorectal cancer; Early diagnosis; Quantitative PCR.

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Figures

**Fig. 1**
Workflow Charts. CRC = colorectal cancer. CEA = carcinoembryonic antigen.

**Fig. 2**
The fecal relative abundance of *C. symbiosum* and *F. nucleatum* among groups. (a) *F. nucleatum* for test cohort. (b) *C. symbiosum* for test cohort. CRC = colorectal cancer. *C. symbiosum* = *clostridium symbiosum*. *F. nucleatum* = *fusobacteria nucleatum*. **P < 0.01.

**Fig. 3**
The diagnostic power of *C. symbiosum* in advanced adenoma and early stage CRC (cancers confined in submucosa including high-grade intraepithelial neoplasia). (a) AUC comparison for *C. symbiosum* abundance with FIT or with CEA in advanced adenoma. (b) AUC comparison for *C. symbiosum* abundance with FIT or with CEA in early stage CRC. (c) Sensitivity for *C. symbiosum* abundance, CEA and FIT test in advanced adenoma. (d) Sensitivity for *C. symbiosum* abundance, CEA and FIT test in early stage CRC. CRC = colorectal cancer. Cs = *Clostridium symbiosum*. Fn = *Fusobacteria nucleatum*. CEA = carcinoembryonic antigen. FIT = fecal immunochemical test. AUC = Area under curve for receiver operating characteristic curve. *P < 0.05. **P < 0.01.

**Fig. 4**
The comparison of ROC for different markers in advanced adenoma, early stage CRC (cancers confined in submucosa including high-grade intraepithelial neoplasia) and all stage CRC. (a) AUC for *C. symbiosum* and *F. nucleatum* abundance in test and validation cohort in advanced adenoma. (b) AUC for Cs + FIT, FIT, *C. symbiosum* and *F. nucleatum* abundance in test and validation cohort in early stage CRC. (c) AUC for BAC + FIT, FIT, *C. symbiosum* and *F. nucleatum* abundance in test cohort and validation in all stage CRC for subjects with FIT results (upper figures) and for subjects with both FIT and CEA tests (lower figures). CRC = colorectal cancer. Cs = *Clostridium symbiosum*. Fn = *Fusobacteria nucleatum*. CEA = carcinoembryonic antigen. FIT = fecal immunochemical test. Cs + FIT = marker combined *C. symbiosum* and FIT. BAC + ALL = marker combined *C. symbiosum* and *F. nucleatum* abundance with FIT and CEA test. BAC + FIT = marker combined *C. symbiosum* and *F. nucleatum* abundance with FIT test. AUC = Area under curve for receiver operating characteristic curve. *P < 0.05. **P < 0.01.

See this image and copyright information in PMC

Comment in

Less Invasive Screening for Colorectal Cancer by Microbiota Analysis: Is it a Reality or an Illusion?
Onodera H. Onodera H. EBioMedicine. 2017 Nov;25:5-6. doi: 10.1016/j.ebiom.2017.10.020. Epub 2017 Oct 19. EBioMedicine. 2017. PMID: 29102292 Free PMC article. No abstract available.

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

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

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