Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers: A Systematic Review and Meta-Analysis

Paige Druce, Natalia Calanzani, Claudia Snudden, Kristi Milley, Rachel Boscott, Dawnya Behiyat, Javiera Martinez-Gutierrez, Smiji Saji, Jasmeen Oberoi, Garth Funston, Mike Messenger, Fiona M. Walter, Jon Emery

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3032-3065
Number of pages34
JournalAdvances in Therapy
Volume38
Issue number6
Early online date27 Apr 2021
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Biomarkers
  • Clinical practice
  • Colorectal cancer
  • Early detection
  • Lower gastrointestinal cancers
  • Primary care

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