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      Plasma levels of microRNA-24, microRNA-320a, and microRNA-423-5p are potential biomarkers for colorectal carcinoma

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          Abstract

          Background

          MicroRNAs are stable and easy to detect in plasma. The plasma levels of microRNAs are often changed in disease conditions, including cancer. This makes circulating microRNAs a novel class of biomarkers for cancer diagnosis. Analyses of online microRNA data base revealed that expression level of three microRNAs, microRNA-24 (miR-24), microRNA-320a (miR-320a), and microRNA-423-5p (miR-423-5p) were down-regulated in colorectal cancer (CRC). However, whether the plasma level of these three microRNAs can serve as biomarkers for CRC diagnosis and prognosis is not determined.

          Methods

          Plasma samples from 223 patients with colorectal related diseases (111 cancer carcinoma, 59 adenoma, 24 colorectal polyps and 29 inflammatory bowel disease) and 130 healthy controls were collected and subjected to reverse transcription-quantitative real time PCR (RT-qPCR) analyses for the three microRNAs. In addition, plasma samples from 43 patients were collected before and after surgical treatment for the same RT-qPCR analyses.

          Results

          The concentrations of plasma miR-24, miR-320a and miR-423-5p were all decreased in patients with CRC and benign lesions (polyps and adenoma) compared with healthy controls, but increased in inflammatory bowel disease (IBD). The sensitivity of miR-24, miR-320a and miR-423-5p for early stage of CRC were 77.78 %, 90.74 %, and 88.89 %, respectively. Moreover, the plasma concentration of the three microRNAs was increased in patients after the surgery who had clinical improvement.

          Conclusions

          The plasma levels of miR-24, miR-320a, and miR-423-5p have promising potential to serve as novel biomarkers for CRC detection, especially for early stage of CRC, which are superior to the currently used clinical biomarkers for CRC detection, such as CEA and CA19-9. Further efforts to develop the three microRNAs as biomarkers for early CRC diagnosis and prediction of surgical treatment outcomes are warrant.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13046-015-0198-6) contains supplementary material, which is available to authorized users.

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          Most cited references26

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          Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.

          Bernard Levin, David Lieberman, Beth McFarland … (2008)
          In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that primarily is effective at early cancer detection and a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.
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            Circulating Exosomal microRNAs as Biomarkers of Colon Cancer

            Hiroko Ogata-Kawata, Masashi Izumiya, Daisuke Kurioka … (2014)
            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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              MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway.

              Eric I-Chao Chang, Shauh-Der Yeh, I-Chang Hsieh … (2013)
              Prostate cancer (PCa) is a leading cause of mortality and morbidity in men worldwide, and emerging evidence suggests that the CD44(high) prostate tumor-initiating cells (TICs) are associated with its poor prognosis. Although microRNAs are frequently dysregulated in human cancers, the influence of microRNAs on PCa malignancy and whether targeting TIC-associated microRNAs inhibit PCa progression remain unclear. In this study, we found that miR-320 is significantly downregulated in PCa. Overexpression of miR-320 in PCa cells decreases PCa tumorigenesis in vitro and in vivo. Global gene expression profiling of miR-320-overexpressing PCa cells reveals that downstream target genes of Wnt/β-catenin pathway and cancer stem cell markers are significantly decreased. MicroRNA-320 inhibits β-catenin expression by targeting the 3'-untranslated region of β-catenin mRNA. The reduction of miR-320 associated with increased β-catenin was also found in CD44(high) subpopulation of prostate cancer cells and clinical PCa specimens. Interestingly, knockdown of miR-320 significantly increases the cancer stem-like properties, such as tumorsphere formation, chemoresistance and tumorigenic abilities, although enriching the population of stem-like TICs among PCa cells. Furthermore, increased miR-320 expression in prostate stem-like TICs significantly suppresses stem cell-like properties of PCa cells. These results support that miR-320 is a key negative regulator in prostate TICs, and suggest developing miR-320 as a novel therapeutic agent may offer benefits for PCa treatment.
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                Author and article information

                Contributors
                Zanxi Fang: fangzanxi@163.com
                Jing Tang: 416695129@qq.com
                Yongying Bai: 627410356@qq.com
                Huayue Lin: sophie.lin07@gmail.com
                Hanyu You: 939113915@qq.com
                Hongwei Jin: 296146742@qq.com
                Lingqing Lin: doralam07@163.com
                Pan You: xmxiamen@aliyun.com
                Juan Li: leeleejuan@qq.com
                Zhang Dai: dzdzdz1983@qq.com
                Xianming Liang: 178292958@qq.com
                Yuanhui Su: 740033835@qq.com
                Qing Hu: 541437602@qq.com
                Fen Wang: fwang@ibt.tmc.edu
                Zhong-Ying Zhang: zhangzy1121@xmu.edu.cn
                Journal
                Journal ID (nlm-ta): J Exp Clin Cancer Res
                Journal ID (iso-abbrev): J. Exp. Clin. Cancer Res
                Title: Journal of Experimental & Clinical Cancer Research : CR
                Publisher: BioMed Central (London )
                ISSN (Print): 0392-9078
                ISSN (Electronic): 1756-9966
                Publication date (Electronic): 22 August 2015
                Publication date PMC-release: 22 August 2015
                Publication date Collection: 2015
                Volume: 34
                Issue: 1
                Electronic Location Identifier: 86
                Affiliations
                [ ]Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China
                [ ]General Hospital of the Yangtze River Shipping, Wuhan, China
                [ ]State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China
                [ ]Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX USA
                Article
                Publisher ID: 198
                DOI: 10.1186/s13046-015-0198-6
                PMC ID: 4546358
                PubMed ID: 26297223
                SO-VID: 48bbf91d-beb0-4348-b068-c3fca8ea5545
                Copyright © © Fang et al. 2015
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 17 April 2015
                Date accepted : 29 July 2015
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: microrna,plasma,colorectal cancer,biomarker,diagnosis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: microrna, plasma, colorectal cancer, biomarker, diagnosis

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