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      Clinical significance of exosomes as potential biomarkers in cancer

      research-article
      Author(s): ,
      Publication date (Electronic):
      Journal: World Journal of Clinical Cases
      Publisher: Baishideng Publishing Group Inc
      Keywords: Exosome, Biomarker, Cancer, Diagnosis, Prognosis

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          Abstract

          BACKGROUND

          Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.

          AIM

          To summarize the performance of exosomal biomarkers in cancer diagnosis and prognosis.

          METHODS

          Relevant publications in the literature were identified by search of the “PubMed” database up to September 11, 2018. The quality of the included studies was assessed by QUADAS-2 and REMARK. For assessment of diagnostic biomarkers, 47 biomarkers and 2240 patients from 30 studies were included.

          RESULTS

          Our results suggested that these exosomal biomarkers had excellent diagnostic ability in various types of cancer, with good sensitivity and specificity. For assessment of prognostic markers, 50 biomarkers and 4797 patients from 42 studies were included. We observed that exosomal biomarkers had prognostic values in overall survival, disease-free survival and recurrence-free survival.

          CONCLUSION

          Exosomes can function as potential biomarkers in cancer diagnosis and prognosis.

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

          Javier Zamora, Víctor Abraira, Alfonso Muriel … (2006)
          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 .
          Article 0 comments Cited 577 times – based on 0 reviews     Review now
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            • Record: found
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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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              Exosome mediated communication within the tumor microenvironment.

              Lara Milane, Amit Singh, GEORGE MATTHEOLABAKIS … (2015)
              It is clear that exosomes (endosome derived vesicles) serve important roles in cellular communication both locally and distally and that the exosomal process is abnormal in cancer. Cancer cells are not malicious cells; they are cells that represent 'survival of the fittest' at its finest. All of the mutations, abnormalities, and phenomenal adaptations to a hostile microenvironment, such as hypoxia and nutrient depletion, represent the astute ability of cancer cells to adapt to their environment and to intracellular changes to achieve a single goal - survival. The aberrant exosomal process in cancer represents yet another adaptation that promotes survival of cancer. Cancer cells can secrete more exosomes than healthy cells, but more importantly, the content of cancer cells is distinct. An illustrative distinction is that exosomes derived from cancer cells contain more microRNA than healthy cells and unlike exosomes released from healthy cells, this microRNA can be associated with the RNA-induced silencing complex (RISC) which is required for processing mature and biologically active microRNA. Cancer derived exosomes have the ability to transfer metastatic potential to a recipient cell and cancer exosomes function in the physical process of invasion. In this review we conceptualize the aberrant exosomal process (formation, content selection, loading, trafficking, and release) in cancer as being partially attributed to cancer specific differences in the endocytotic process of receptor recycling/degradation and plasma membrane remodeling and the function of the endosome as a signaling entity. We discuss this concept and, to advance comprehension of exosomal function in cancer as mediators of communication, we detail and discuss exosome biology, formation, and communication in health and cancer; exosomal content in cancer; exosomal biomarkers in cancer; exosome mediated communication in cancer metastasis, drug resistance, and interfacing with the immune system; and discuss the therapeutic manipulation of exosomal content for cancer treatment including current clinical trials of exosomal therapeutics. Often referred to as cellular nanoparticles, understanding exosomes, and how cancer cells use these cellular nanoparticles in communication is at the cutting edge frontier of advancing cancer biology.
              Article 0 comments Cited 326 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Chi-Hin Wong
                Yang-Chao Chen
                Journal
                Journal ID (nlm-ta): World J Clin Cases
                Journal ID (publisher-id): WJCC
                Title: World Journal of Clinical Cases
                Publisher: Baishideng Publishing Group Inc
                ISSN (Electronic): 2307-8960
                Publication date (Print): 26 January 2019
                Publication date (Electronic): 26 January 2019
                Volume: 7
                Issue: 2
                Pages: 171-190
                Affiliations
                School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
                School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
                Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. yangchaochen@ 123456cuhk.edu.hk
                Author notes

                Author contributions: Chen YC and Wong CH wrote the paper.

                Corresponding author: Yang-Chao Chen, PhD, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. yangchaochen@ 123456cuhk.edu.hk

                Telephone: +852-39431100 Fax: +852-26035123

                Article
                Other ID: jWJCC.v7.i2.pg171
                DOI: 10.12998/wjcc.v7.i2.171
                PMC ID: 6354096
                PubMed ID: 30705894
                SO-VID: 773ed24e-1f61-4dd4-9673-2bff56394edf
                Copyright © ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
                License:

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                Date received : 25 October 2018
                Date revision received : 27 December 2018
                Date accepted : 3 January 2019
                Categories
                Subject: Systematic Review

                Keywords: exosome,biomarker,cancer,diagnosis,prognosis
                Data availability:
                Keywords: exosome, biomarker, cancer, diagnosis, prognosis

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