Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastroi
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REVIEW
Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review Natalia Calanzani
. Paige E. Druce . Claudia Snudden . Kristi M. Milley .
Rachel Boscott . Dawnya Behiyat . Smiji Saji . Javiera Martinez-Gutierrez . Jasmeen Oberoi . Garth Funston . Mike Messenger . Jon Emery . Fiona M. Walter Received: October 5, 2020 / Accepted: November 11, 2020 Ó The Author(s) 2020
ABSTRACT Introduction: Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often nonspecific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to Electronic Supplementary Material The online version of this article (https://doi.org/10.1007/s12325020-01571-z) contains supplementary material, which is available to authorized users. N. Calanzani (&) C. Snudden R. Boscott D. Behiyat S. Saji G. Funston J. Emery F. M. Walter The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK e-mail: [email protected] P. E. Druce K. M. Milley J. Martinez-Gutierrez J. Oberoi J. Emery F. M. Walter Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia J. Martinez-Gutierrez Department of Family Medicine, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile M. Messenger Leeds Centre for Personalised Medicine and Health, University of Leeds, Leeds, UK
identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. Methods: We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. Results: We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and
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