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

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. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01645-6.

The Importance of Evaluating Serum Levels of Tumor Markers M2-PK and Inhibin A in Patients Undergoing Colonoscopy

“…The occurrence of an increase in M2-PK level status is frequently observed in patients with cancer (both solid and hematological malignancies) which could be resulted from the effect of the tumor cell activity on the glycolytic and metabolic system. [20][21][22] The findings of the high level of M2-PK state in this study agree with previous reports on colorectal cancer patients. [23][24][25][26] An increased amount of inflammatory cytokines, released in response to the tumor and changing the metabolic process of transformed cells in the early stages of polypogenesis and tumorigenesis play an important role in the metabolic system activation in the early stage of colorectal cancer patients.…”

“…The occurrence of an increase in M2-PK level status is frequently observed in patients with cancer (both solid and hematological malignancies) which could be resulted from the effect of the tumor cell activity on the glycolytic and metabolic system. 20 – 22 The findings of the high level of M2-PK state in this study agree with previous reports on colorectal cancer patients. 23 – 26 …”

Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges

“…The forest plots were edited using GraphPad Prism software. Heterogeneity and threshold effects were evaluated using the visual summary of SROC plots and random effects correlation, as described by Druce et al [ 79 ]. All summary parameters were calculated along with the associated 95% confidence interval (CI).…”