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

Abstract

Introduction Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, 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 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 PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. Conclusion Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01571-z) contains supplementary material, which is available to authorized users.

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

“…These have been reported elsewhere [12]. The protocol for this review was registered on PROSPERO (registration ID CRD42020165005) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) statement was followed [13].…”

Emerging roles of non‑coding RNAs in the response of rectal cancer to radiotherapy (Review)

“…Most studies involve a small number of samples with no validation group (123)(124)(125). The investigations involving small cohorts are associated with a high risk of false-positive cases, which has hindered or delayed the clinical application of diagnostic and prognostic biomarkers (126). To overcome these limitations, Azizian et al (127) performed microarray analysis of a training set comprising 45 preoperative biopsies from patients with rectal cancer to identify potential miRNAs that can predict tumor regression grade and other clinical parameters.…”

Risk stratification of pancreatic cancer by a blood test for apolipoprotein A2-isoforms

“…This study highlights the need for more biomarker studies that consider the primary care/community setting as their intended population. It suggested that apoA2-ATQ/AT and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic cancer and gastric cancer, respectively [ 23 ].…”