43
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Examining plasma microRNA markers for colorectal cancer at different stages

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Circulating microRNAs (miRNAs) have emerged as promising biomarkers; however, few miRNAs have been reproducible and can be used in clinical practice. In this study, we screened the levels of 754 miRNAs using TaqMan array in 50 individual plasma samples from 10 demographically matched healthy controls and 40 colorectal cancer (CRC) patients (10 each of stage I–IV) and identified 22 miRNAs associated with the presence of and stages of CRC. Then we performed the validation for 11 miRNAs in an independent cohort including 187 CRC cases and 47 healthy controls. Comprehensive analyses showed that plasma miR-96 distinguished stage I–IV CRC from healthy controls with an area under curve (AUC) of 0.740; miR-203 separated stage III–IV CRC patients from stage I–II with an AUC of 0.757; and miR-141 differentiated stage IV CRC from stage I–III patients with an AUC of 0.851. Survival analyses showed that plasma miR-96 and miR-200b were independent prognostic factors for overall survival. Thus, we propose four miRNAs (miR-96, miR-203, miR-141 and miR-200b) as clinically validated circulating biomarkers for CRC prognosis that warrant further evaluation for clinical utility.

          Related collections

          Most cited references54

          • Record: found
          • Abstract: found
          • Article: not found

          Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer.

          MicroRNA (miRNA) opens up a new field for molecular diagnosis of cancer. However, the role of circulating miRNAs in plasma/serum in cancer diagnosis is not clear. The aim of this study was to investigate whether plasma miRNAs can be used as biomarkers for the early detection of colorectal carcinoma (CRC). We measured the levels of 12 miRNAs (miR-134, -146a, -17-3p, -181d, -191, -221, -222, -223, -25, -29a, -320a and -92a) in plasma samples from patients with advanced colorectal neoplasia (carcinomas and advanced adenomas) and healthy controls using real-time RT-PCR. We found that plasma miR-29a and miR-92a have significant diagnostic value for advanced neoplasia. MiR-29a yielded an AUC (the areas under the ROC curve) of 0.844 and miR-92a yielded an AUC of 0.838 in discriminating CRC from controls. More importantly, these 2 miRNAs also could discriminate advanced adenomas from controls and yielded an AUC of 0.769 for miR-29a and 0.749 for miR-92a. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.883 with 83.0% sensitivity and 84.7% specificity in discriminating CRC, and AUC of 0.773 with 73.0% sensitivity and 79.7% specificity in discriminating advanced adenomas. Collectively, these data suggest that plasma miR-29a and miR-92a have strong potential as novel noninvasive biomarkers for early detection of CRC.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            miR-221 overexpression contributes to liver tumorigenesis.

            MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

              MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia.
                Bookmark

                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                8 March 2016
                4 February 2016
                : 7
                : 10
                : 11434-11449
                Affiliations
                1 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                2 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                3 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                4 The Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                5 Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
                Author notes
                Correspondence to: Wei Zhang, wzhang@ 123456mdanderson.org
                Article
                7196
                10.18632/oncotarget.7196
                4905484
                26863633
                f0e0f4db-911d-4fed-82e8-93e01f4da0da
                Copyright: © 2016 Sun et al.

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

                History
                : 23 September 2015
                : 23 January 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                microrna,biomarker,plasma,colorectal cancer,stage
                Oncology & Radiotherapy
                microrna, biomarker, plasma, colorectal cancer, stage

                Comments

                Comment on this article