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      Matrix metalloproteinase‑1 and microRNA‑486‑5p in urinary exosomes can be used to detect early lung cancer: A preliminary report

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          Abstract

          The present study describes a novel molecular-genetic method suitable for lung cancer (LC) screening in the work-place and at community health centers. Using urinary-isolated exosomes from 35 patients with LC and 40 healthy volunteers, the expression ratio of MMP-1/CD63, and the relative expression levels of both microRNA (miRNA)-21 and miRNA-486-5p were measured. MMP-1/CD63 expression ratio was significantly higher in patients with LC than in the healthy controls {1.342 [95% confidence interval (CI): 0.890–1.974] vs. 0.600 (0.490–0.900); P<0.0001}. The relative expression of miRNA-486-5p in male healthy controls was significantly different from that in female healthy controls, whereas there was no significant difference in miRNA-21. Receiver operating characteristic curve (ROC) analysis of MMP-1/CD63 showed 92.5% sensitivity and 54.3% specificity, whereas miRNA-486-5p showed 85% sensitivity and 70.8% specificity for men, and 70.0% sensitivity and 72.7% specificity for women. The logistic regression model used to evaluate the association of LC with the combination of MMP-1/CD63 and miRNA-486-5p revealed that the area under the ROC curve was 0.954 (95% CI: 0.908–1.000), and the model had 89% sensitivity and 88% specificity after adjusting for age, sex and smoking status. These data suggested that the combined analysis of MMP-1/CD63 and miRNA-486-5p in urinary exosomes may be used to detect patients with early-stage LC in the work-place and at community health centers, although confirmational studies are warranted.

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          Most cited references52

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            NIH Image to ImageJ: 25 years of image analysis

            For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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              Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

              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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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                March 2024
                29 January 2024
                29 January 2024
                : 27
                : 3
                : 127
                Affiliations
                [1 ]Department of Clinical Pharmacy, Center for Clinical Pharmacy and Sciences, Kitasato University School of Pharmacy, Tokyo 108-8641, Japan
                [2 ]Department of General Thoracic Surgery, Jichi Medical University Saitama Medical Center, Saitama 330-0834, Japan
                [3 ]Center for Respiratory Diseases, International University of Health and Welfare Hospital, Nasu-Shiobara, Tochigi 329-2763, Japan
                [4 ]Department of Chest Surgery, International University of Health and Welfare Hospital, Nasu-Shiobara, Tochigi 329-2763, Japan
                [5 ]Biomedical Laboratory, Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
                [6 ]Basic Clinical Science and Public Health, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
                [7 ]Department of Internal Medicine, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
                [8 ]Department of Internal Medicine, International University of Health and Welfare Hospital, Nasu-Shiobara, Tochigi 329-2763, Japan
                [9 ]Department of Preventive Medicine, International University of Health and Welfare Hospital, Nasu-Shiobara, Tochigi 329-2763, Japan
                [10 ]Research and Education Center for Clinical Pharmacy, Division of Clinical Pharmacy, Laboratory of Pharmacy Practice and Science 1, Kitasato University School of Pharmacy, Sagamihara, Kanagawa 252-0375, Japan
                [11 ]Department of General Thoracic Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
                [12 ]Department of Health and Welfare, Higashi Nippon International University, Iwaki, Fukushima 970-8023, Japan
                Author notes
                Correspondence to: Dr Wataru Ando, Department of Clinical Pharmacy, Center for Clinical Pharmacy and Sciences, Kitasato University School of Pharmacy, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan, E-mail: andow@ 123456pharm.kitasato-u.ac.jp
                Professor Isao Okazaki, Department of Health and Welfare, Higashi Nippon International University, 37 Suganezawa, Taira Kamata, Iwaki, Fukushima 970-8023, Japan, E-mail: iokazaki@ 123456m.tonichi-kokusai.u.ac.jp
                [*]

                Contributed equally

                Article
                OL-27-3-14261
                10.3892/ol.2024.14261
                10851336
                38333640
                f85a72a8-3b23-4457-873c-d7c0a90cbab1
                Copyright: © Ando et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 01 March 2023
                : 21 December 2023
                Funding
                Funded by: Japanese Society for the Promotion of Science
                Award ID: 18K08797
                This study was supported by the Japanese Society for the Promotion of Science (Kakenhi grant no. 18K08797) given to SI and YK.
                Categories
                Articles

                Oncology & Radiotherapy
                lung cancer screening,urinary exosome,mmp-1,mirna-486-5p
                Oncology & Radiotherapy
                lung cancer screening, urinary exosome, mmp-1, mirna-486-5p

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