Abstract
BackgroundEmerging evidence has revealed miR-29 family as promising biomarkers for colorectal cancer (CRC), but their biomarker potential and molecular mechanisms remain poorly understood.MethodsWe performed a comprehensive meta-analysis to evaluate the biomarker performance of individual miR-29 and the related miRNA combination biomarkers. Meanwhile, we conducted an integrative bioinformatics analysis to unfold the underlying biological function of miR-29 and their relationship with CRC.ResultsUsing miR-29 expression to diagnose CRC produced 0.82 area under the curve, 70% sensitivity and 81% specificity while the combination biomarkers based on miR-29 enhanced the diagnostic power with an AUC of 0.86, a sensitivity of 78% and a specificity of 91%. For the prognosis evaluation, patients with higher expression of miR-29 had better survival outcome (pooled HR 0.78; 95% CI 0.56–1.07). In addition, miR-29 has also been identified as potential biomarker for predicting recurrence and metastasis in CRC. Then the genes regulated by the miR-29 family were retrieved and found closely associated with the molecular pathogenesis of CRC according to the gene ontology and pathway analysis. Furthermore, hub nodes and significant modules were identified from the protein–protein interaction network constructed with miR-29 family targets, which were also confirmed highly involved in the establishment and development of CRC.ConclusionsCurrent evidences suggest miR-29 family may become promising biomarkers for risk, recurrence, metastasis and survival outcome of CRC. Meanwhile our data highlight the potential clinical use of miRNA combination biomarkers. Nevertheless, further prospective studies are warranted before the application of the useful biomarkers in the clinical.
Highlights
Emerging evidence has revealed miR-29 family as promising biomarkers for colorectal cancer (CRC), but their biomarker potential and molecular mechanisms remain poorly understood
Eligibility criteria The eligible studies in this study must meet all the following criteria: (1) the diagnosis of CRC was made based on histopathological confirmation, (2) the associations between miR-29 expression and diagnostic or recurrence or metastasis or survival outcome were measured, and (3) studies directly provided true positive (TP), false positive (FP), false negative (FN), and true negative (TN) for diagnostic studies or hazard ratio (HR) and their 95% confidence intervals (CIs) for prognostic studies or with data available regarding these statistics
We found that pooled studies with large sample size assays showed a higher level of overall accuracy compared with that of small sample size, with a sensitivity of 0.61 versus 0.78, specificity of 0.86 versus 0.73, positive likelihood ratio (PLR) of 4.3 versus 2.9, negative likelihood ratio (NLR) of 0.45 versus 0.30, diagnostic odds ratio (DOR) of 10 versus 10, and area under the summary receiver operating characteristic curve (SROC) curve (AUC) of 0.84 versus 0.82, which indicated that more large-scale prospective studies are warranted
Summary
Emerging evidence has revealed miR-29 family as promising biomarkers for colorectal cancer (CRC), but their biomarker potential and molecular mechanisms remain poorly understood. Several early detection procedures of CRC have been established and are increasingly applied, including fecal occult-blood testing (FOBT), colonoscopy, and stool DNA test [3]. None of these methods has been developed as a optimal or universally accepted strategy due to their low adherence rates, high cost or low sensitivity [4]. Considering the perfect biomarker features and critical involvement in the regulation of developmental, physiological and oncogenic processes, miRNAs show great promises to be convenient and informative for CRC diagnosis, prognosis and therapeutic efficacy
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