TY - JOUR
T1 - Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers
T2 - A Systematic Review and Meta-Analysis
AU - Druce, Paige
AU - Calanzani, Natalia
AU - Snudden, Claudia
AU - Milley, Kristi
AU - Boscott, Rachel
AU - Behiyat, Dawnya
AU - Martinez-Gutierrez, Javiera
AU - Saji, Smiji
AU - Oberoi, Jasmeen
AU - Funston, Garth
AU - Messenger, Mike
AU - Walter, Fiona M.
AU - Emery, Jon
N1 - Funding Information:
This study was supported by the CanTest Collaborative (funded by Cancer Research UK C8640/A23385) of which Fiona M. Walter is Director, Jon Emery is an Associate Director, Mike Messenger is co-investigator, and Natalia Calanzani and Garth Funston are researchers. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Paige Druce, Kristi Milley and Jon Emery are supported by the Cancer Australia Primary Care Collaborative Cancer Clinical Trials Group (PC4). Mike Messenger is funded by the NIHR Leeds In Vitro Diagnostic Co-operative (UK). No Rapid Service Fee or Open Access fee was received by the journal for the publication of this article.
Funding Information:
This study was supported by the CanTest Collaborative (funded by Cancer Research UK C8640/A23385) of which Fiona M. Walter is Director, Jon Emery is an Associate Director, Mike Messenger is co-investigator, and Natalia Calanzani and Garth Funston are researchers. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Paige Druce, Kristi Milley and Jon Emery are supported by the Cancer Australia Primary Care Collaborative Cancer Clinical Trials Group (PC4). Mike Messenger is funded by the NIHR Leeds In Vitro Diagnostic Co-operative (UK). No Rapid Service Fee or Open Access fee was received by the journal for the publication of this article. We thank Veronica Phillips, Assistant Librarian, University of Cambridge Medical Library, and Jim Berryman, Liaison Librarian, Brownless Biomedical Library University of Melbourne for expert input when developing the search strategy. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Mike Messenger has previously held research grants with Roche Diagnostics, Everest Detection Ltd, SomaLogic Inc, Abbott Laboratories, Myriad Genetics, Inivata, Oncimmune, Janssen and Siemens Healthineers and has also received paid consultancy from PinPoint Data Science Ltd and Cepheid Inc in the field of cancer diagnostics. Garth Funston is a current member of the Oncology Editorial Board for Advances in Therapy. Paige Druce, Natalia Calanzani, Claudia Snudden, Kristi Milley, Rachel Boscott, Dawnya Behiyat, Javiera Martinez-Gutierrez, Smiji Saji, Jasmeen Oberoi, Jon Emery and Fiona M Walter have nothing to disclose. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - Introduction:Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations. Methods: We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible. Results: We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6–84.0%) and 88.0% (95% CI 79.1–93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2–86.6%) and specificity of 80.1% (95% CI 76.7–83.0%). Conclusion: Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.
AB - Introduction:Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations. Methods: We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible. Results: We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6–84.0%) and 88.0% (95% CI 79.1–93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2–86.6%) and specificity of 80.1% (95% CI 76.7–83.0%). Conclusion: Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.
KW - Biomarkers
KW - Clinical practice
KW - Colorectal cancer
KW - Early detection
KW - Lower gastrointestinal cancers
KW - Primary care
UR - http://www.scopus.com/inward/record.url?scp=85104895086&partnerID=8YFLogxK
U2 - 10.1007/s12325-021-01645-6
DO - 10.1007/s12325-021-01645-6
M3 - Article
C2 - 33907946
VL - 38
SP - 3032
EP - 3065
JO - Advances in Therapy
JF - Advances in Therapy
SN - 0741-238X
IS - 6
ER -
