Fecal Clostridium symbiosum for Noninvasive Detection of Early and Advanced Colorectal Cancer: Test and Validation Studies
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. In the test stage, the relative abundance of Clostridium symbiosum (C. symbiosum) was measure...
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| Published in | EBioMedicine Vol. 25; no. C; pp. 32 - 40 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.11.2017
Elsevier |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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.
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).
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.
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.
•The fecal abundance of Clostridium symbiosum was found increased in patients with colorectal neoplasia and it may serve as a potiential biomarker in non-invasive early differentiation of colorectal cancer from healthy controls.•The fecal abundance of Clostridium symbiosum was even more sensitive and efficient in diagnosis of both early and advanced colorectal cancer than reported markers like fecal immunochemical test, carcinoembryonic antigen and the abundance of Fusobacterium nucleatum.•Combining the abundance of Clostridium symbiosum and the other markers above may further enhance its predictive performance. |
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| AbstractList | 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. AbstractObjectiveCurrent 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. DesignIn 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). ResultsSignificant 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. ConclusionsFecal 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. 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. 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). 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. 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. •The fecal abundance of Clostridium symbiosum was found increased in patients with colorectal neoplasia and it may serve as a potiential biomarker in non-invasive early differentiation of colorectal cancer from healthy controls.•The fecal abundance of Clostridium symbiosum was even more sensitive and efficient in diagnosis of both early and advanced colorectal cancer than reported markers like fecal immunochemical test, carcinoembryonic antigen and the abundance of Fusobacterium nucleatum.•Combining the abundance of Clostridium symbiosum and the other markers above may further enhance its predictive performance. • The fecal abundance of Clostridium symbiosum was found increased in patients with colorectal neoplasia and it may serve as a potiential biomarker in non-invasive early differentiation of colorectal cancer from healthy controls. • The fecal abundance of Clostridium symbiosum was even more sensitive and efficient in diagnosis of both early and advanced colorectal cancer than reported markers like fecal immunochemical test, carcinoembryonic antigen and the abundance of Fusobacterium nucleatum . • Combining the abundance of Clostridium symbiosum and the other markers above may further enhance its predictive performance. 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. 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). 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. 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. 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.OBJECTIVECurrent 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.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).DESIGNIn 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).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.RESULTSSignificant 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.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.CONCLUSIONSFecal 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. |
| Author | Sun, Xiao-Ming Zou, Tian-Hui Liu, Zhan-Ju Cai, Guo-Xiang Sun, Danfeng Chen, Ying-Xuan Chen, Xiao-Yu Cai, San-Jun Xie, Yuan-Hong Qiu, Yi-Wen Gao, Qin-Yan Xu, Jie Fang, Jing-Yuan Chen, Hui-Min Yu, Si-Yi Cui, Yun Gu, Wei-Qi |
| AuthorAffiliation | a 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 c Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China b Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China |
| AuthorAffiliation_xml | – name: c Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China – name: a 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 – name: b Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China |
| Author_xml | – sequence: 1 givenname: Yuan-Hong surname: Xie fullname: Xie, Yuan-Hong organization: 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 – sequence: 2 givenname: Qin-Yan surname: Gao fullname: Gao, Qin-Yan organization: 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 – sequence: 3 givenname: Guo-Xiang surname: Cai fullname: Cai, Guo-Xiang organization: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China – sequence: 4 givenname: Xiao-Ming surname: Sun fullname: Sun, Xiao-Ming organization: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China – sequence: 5 givenname: Tian-Hui surname: Zou fullname: Zou, Tian-Hui organization: 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 – sequence: 6 givenname: Hui-Min surname: Chen fullname: Chen, Hui-Min organization: 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 – sequence: 7 givenname: Si-Yi surname: Yu fullname: Yu, Si-Yi organization: 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 – sequence: 8 givenname: Yi-Wen surname: Qiu fullname: Qiu, Yi-Wen organization: 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 – sequence: 9 givenname: Wei-Qi surname: Gu fullname: Gu, Wei-Qi organization: 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 – sequence: 10 givenname: Xiao-Yu surname: Chen fullname: Chen, Xiao-Yu organization: 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 – sequence: 11 givenname: Yun surname: Cui fullname: Cui, Yun organization: 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 – sequence: 12 givenname: Danfeng surname: Sun fullname: Sun, Danfeng organization: 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 – sequence: 13 givenname: Zhan-Ju surname: Liu fullname: Liu, Zhan-Ju organization: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China – sequence: 14 givenname: San-Jun surname: Cai fullname: Cai, San-Jun email: csj@shca.org.cn organization: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China – sequence: 15 givenname: Jie orcidid: 0000-0001-9163-3898 surname: Xu fullname: Xu, Jie email: jiexu@sjtu.edu.cn organization: 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 – sequence: 16 givenname: Ying-Xuan surname: Chen fullname: Chen, Ying-Xuan email: yingxuanchen71@sjtu.edu.cn organization: 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 – sequence: 17 givenname: Jing-Yuan surname: Fang fullname: Fang, Jing-Yuan email: jingyuanfang@sjtu.edu.cn organization: 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 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29033369$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | 2017 Copyright © 2017. Published by Elsevier B.V. 2017 Published by Elsevier B.V. 2017 |
| Copyright_xml | – notice: 2017 – notice: Copyright © 2017. Published by Elsevier B.V. – notice: 2017 Published by Elsevier B.V. 2017 |
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| Keywords | Clostridium symbiosum Early diagnosis Quantitative PCR Colorectal cancer |
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| Snippet | Current non-invasive early detection of colorectal cancer (CRC) requires improvement. We aimed to identified a fecal Clostridium symbiosum-based biomarker for... AbstractObjectiveCurrent non-invasive early detection of colorectal cancer (CRC) requires improvement. We aimed to identified a fecal Clostridium... • The fecal abundance of Clostridium symbiosum was found increased in patients with colorectal neoplasia and it may serve as a potiential biomarker in... Objective: Current non-invasive early detection of colorectal cancer (CRC) requires improvement. We aimed to identified a fecal Clostridium symbiosum-based... |
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| SubjectTerms | Adult Advanced Basic Science Aged Aged, 80 and over Biomarkers, Tumor - blood Biomarkers, Tumor - isolation & purification Clostridium symbiosum Clostridium symbiosum - genetics Clostridium symbiosum - isolation & purification Colonoscopy Colorectal cancer Colorectal Neoplasms - blood Colorectal Neoplasms - diagnosis Colorectal Neoplasms - microbiology Colorectal Neoplasms - pathology Early Detection of Cancer Early diagnosis Feces - microbiology Female Fusobacterium nucleatum - genetics Fusobacterium nucleatum - isolation & purification Gastrointestinal Microbiome - genetics Humans Internal Medicine Male Middle Aged Occult Blood Predictive Value of Tests Quantitative PCR Research Paper |
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| Title | Fecal Clostridium symbiosum for Noninvasive Detection of Early and Advanced Colorectal Cancer: Test and Validation Studies |
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