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      The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis

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          Abstract

          This systematic analysis aimed to investigate the value of microRNA-21 (miR-21) in colorectal cancer for multiple purposes, including diagnosis and prognosis, as well as its predictive power in combination biomarkers. Fifty-seven eligible studies were included in our meta-analysis, including 25 studies for diagnostic meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta-analysis of miR-21 alone, the overall pooled results for sensitivity, specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85 (0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89), respectively. For the diagnostic meta-analysis of miR-21-related combination biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87), and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that miRNA combination markers in circulation exhibited high predictive power, with sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92 (0.89-0.94). For the prognostic meta-analysis, patients with higher expression of miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio (HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93), respectively. Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a prognostic marker for colorectal cancer. In addition, miRNA combination biomarkers may provide a new approach for clinical application.

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          Most cited references57

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          Meta-DiSc: a software for meta-analysis of test accuracy data

          Background Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. Results Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. Conclusion Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at .
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            MicroRNAs in cancer.

            MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs), controlling genes involved in cellular processes such as inflammation, cell-cycle regulation, stress response, differentiation, apoptosis, and migration. Thus, miRNAs have been implicated in the regulation of virtually all signaling circuits within a cell, and their dysregulation has been shown to play an essential role in the development and progression of cancer. Here, after a brief description of miRNA genomics, biogenesis, and function, we discuss the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies.
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              Circulating Exosomal microRNAs as Biomarkers of Colon Cancer

              Purpose Exosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. Experimental Design Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. Results The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. Conclusion Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                4 July 2017
                22 March 2017
                : 8
                : 27
                : 44893-44909
                Affiliations
                1 Department of Radiotherapy & Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China
                2 Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
                3 Suzhou Key Laboratory for Radiation Oncology, Suzhou, China
                4 Center for Systems Biology, Soochow University, Suzhou, China
                5 School of Medicine, Örebro University, Örebro, Sweden
                Author notes
                Correspondence to: Yaqun Zhu, szzhuyaqun@ 123456sina.com
                Article
                16488
                10.18632/oncotarget.16488
                5546529
                28415652
                da0b5201-bcae-42ec-a7f3-a3bba36e0b5c
                Copyright: © 2017 Peng et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 September 2016
                : 14 March 2017
                Categories
                Review

                Oncology & Radiotherapy
                mir-21,diagnosis,prognosis,colorectal cancer,meta-analysis
                Oncology & Radiotherapy
                mir-21, diagnosis, prognosis, colorectal cancer, meta-analysis

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