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      • Record: found
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      Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer

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          Abstract

          Background

          Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC).

          Methods

          In total, 55 individuals were enrolled, comprising healthy ( n = 21) and EOC subjects ( n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity.

          Results

          Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p<0.0001) and could be a potential biomarker for monitoring the EOC progression from early stage to late stage ( p = 0.018).

          Conclusions

          Plasma derived exosomal miR-4732-5p may be a promising candidate biomarker for diagnosing EOC.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13048-021-00814-z.

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          Most cited references69

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          Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

          Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)
          Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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            MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

            Rajesha Rupaimoole, Frank J Slack (2017)
            MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic.
            Article 0 comments Cited 1379 times – based on 0 reviews     Review now
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              Ovarian cancer statistics, 2018

              Lindsey A Torre, Britton Trabert, Carol DeSantis … (2018)
              In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.
              Article 0 comments Cited 1015 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Youn Jin Choi: yunno@catholic.ac.kr
                Journal
                Journal ID (nlm-ta): J Ovarian Res
                Journal ID (iso-abbrev): J Ovarian Res
                Title: Journal of Ovarian Research
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1757-2215
                Publication date (Electronic): 28 April 2021
                Publication date PMC-release: 28 April 2021
                Publication date Collection: 2021
                Volume: 14
                Electronic Location Identifier: 59
                Affiliations
                [1 ]GRID grid.411947.e, ISNI 0000 0004 0470 4224, Department of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, College of Medicine, , The Catholic University of Korea, ; Seoul, Republic of Korea
                [2 ]GRID grid.411947.e, ISNI 0000 0004 0470 4224, Cancer Research Institute, College of Medicine, , The Catholic University of Korea, ; Seoul, Republic of Korea
                [3 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Obstetrics and Gynecology, Affiliated Hangzhou First People’s Hospital, , Zhejiang University School of Medicine, ; Hangzhou, China
                Article
                Publisher ID: 814
                DOI: 10.1186/s13048-021-00814-z
                PMC ID: 8082916
                PubMed ID: 33910598
                SO-VID: bc61bf91-21f2-44e1-9dfc-d9461b3676f3
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                Date received : 19 February 2021
                Date accepted : 20 April 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: 2016R1D1A1B04932862
                Award ID: 2018M3A9E8021512
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Obstetrics & Gynecology
                Keywords: exosomes,exosomal mirna profiling,micrornas,epithelial ovarian cancer,mir-4732-5p
                Data availability:
                ScienceOpen disciplines: Obstetrics & Gynecology
                Keywords: exosomes, exosomal mirna profiling, micrornas, epithelial ovarian cancer, mir-4732-5p

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