Systematic literature review and clinical validation of circulating microRNAs as diagnostic biomarkers for colorectal cancer

Abstract

Because patients with colorectal cancer (CRC) are usually diagnosed at an advanced stage and current serum tumor markers have limited diagnostic efficacy, there is an urgent need to identify reliable diagnostic biomarkers. To better define the diagnostic potential of microRNAs (miRNAs) for CRC, we performed a comprehensive evaluation of reported circulating CRC miRNA markers. After a systematic literature review, we selected 30 candidate miRNAs and used quantitative real-time polymerase chain reaction to examine their expression in a training cohort of 120 plasma samples (CRC vs healthy controls (HC) = 60:60). Expression data was confirmed in a validation cohort of 160 plasma samples (CRC vs HC = 80:80). We ultimately identified 5 dysregulated circulating miRNAs (miR-15b, miR-17, miR-21, miR-26b, and miR-145), of which miR-21 and miR-26b proved to have the best diagnostic performance in the training and validation cohorts, respectively. Based on these results, we propose a novel blood-based diagnostic model, integrating 5 CRC-related miRNAs and serum carcinoembryonic antigen (CEA), which provides better diagnostic performance than the combined 5 miRNAs, CEA alone, or any single miRNA. We propose that the novel CRC diagnostic model presented here will be useful for overcoming the limitations faced by current non-invasive diagnostic strategies.

Phenotypic miRNA Screen Identifies miR-26b to Promote the Growth and Survival of Endothelial Cells

“…Previous studies have demonstrated that the expression level of miR-26b is reduced in the tissues of many cancers of liver, 40 breast, 41 and colon. 42 Functionally, miR-26b exerts a tumor-suppressive role in many types of cancer, and the miR-26b-mediated growth inhibition is achieved through suppression of target genes like OCT4, 43 SMAD1, CTGF, 44 and/or COX2. 45 In contrast, overexpression of miR-26a in a murine glioma model enhances de novo tumor formation.…”

Circulating microRNAs as Biomarkers of Radiation Exposure: A Systematic Review and Meta-Analysis

“…15 Although it has been shown that the profile of circulating miRNAs has both diagnostic and prognostic potential, 17,18 recent works have confirmed inconsistency among multiple studies. 19,20 The authors suggest that this phenomenon could be explained by (1) utilization of different profiling methodologies, (2) small study groups, (3) greatly increased risk for type 1 error owing to the problem of multiple comparisons, and (4) confounding clinical effects affecting the responsiveness of miRNA expression to radiation-specific stimuli. Inconsistencies in circulating miRNAs in oncology studies can be also explained by methodological bias 21 and the overlapping effect of many physiological and pathophysiological processes, 22 but also by the different animal species used in the studies and highly heterogeneous study models (ie, different doses of radiation, irradiated sites, and assessed timepoints), and thus these inconsistencies require a systematic analysis of the results.…”

A comprehensive study of immunology repertoires in both preoperative stage and postoperative stage in patients with colorectal cancer

“…As the 3rd leading cause of tumor mortality, colorectal cancer is a well-known and well-studied type of cancer. The previous studies on colorectal cancer's biomarkers, surgery methods, metastatic mechanisms, target medicine-related researches, anesthesia methods, immune repertoires, all have revealed the fundamental data (Daher, Chouillard, & Panis, 2014;Deschoolmeester, Baay, Specenier, Lardon, & Vermorken, 2010;Pan et al, 2017;Tsai et al, 2010). Here, we recruited 19 CRC patients and five healthy controls to study the difference in immune repertoire status among colorectal cancer patient at preoperative, postoperative, and healthy controls.…”