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      A test of miR-128-3p and miR-33a-5p in serum exosome as biomarkers for auxiliary diagnosis of non-small cell lung cancer

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          Abstract

          Background

          Lung cancer is the malignant tumor with the highest incidence and mortality rate in the world today, and non-small cell lung cancer (NSCLC) is its most common type. However, there is still a paucity of specific tumor markers for lung cancer screening. Herein, we detected and compared the levels of miR-128-3p and miR-33a-5p in serum exosomes of NSCLC patients and healthy volunteers, with the aim of identifying suitable exosomal microRNAs (miRNAs) as tumor biomarkers, and explored their value in the auxiliary diagnosis of NSCLC.

          Methods

          All participants were recruited from September 1, 2022 to December 30, 2022, and met the inclusion criteria. The case group included 20 patients with lung nodules who were highly suspected of having lung cancer (two cases were excluded). A total of 18 healthy volunteers (control group) were also enrolled. Blood samples were collected in both the case group before surgery and in the control group. Quantitative real-time polymerase chain reaction method was used to detect the expression of miR-128-3p and miR-33a-5p in serum exosomes. The main indicators of statistical analysis included the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

          Results

          Compared with the healthy control group, the NSCLC case group had significantly lower expression levels of serum exosome miR-128-3p and miR-33a-5p (P<0.01, P<0.001), and there was a significant positive correlation between the two exosome miRNAs (r=0.848, P<0.01). The AUC values of miR-128-3p alone and miR-33a-5p alone in distinguishing case group and control group were 0.789 [95% confidence interval (CI): 0.637–0.940; sensitivity: 61.1%; specificity: 94.4%; P=0.003] and 0.821 (95% CI: 0.668–0.974; sensitivity: 77.8%; specificity: 83.3%; and P=0.001), respectively. The combination of miR-128-3p and miR-33a-5p had an AUC of 0.855 (95% CI: 0.719–0.991; P<0.001) for distinguishing case group and control group, which was greater than the AUC values of miR-128-3p alone and miR-33a-5p alone (cut-off value: 0.034; sensitivity: 83.3%; and specificity: 88.9%). However, there was no significant difference in the AUC among these three groups (P>0.05).

          Conclusions

          Serum exosome miR-128-3p and miR-33a-5p showed good performance in NSCLC screening and may be used as new biomarkers for large-scale NSCLC screening.

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          Most cited references39

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          Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

          Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Funding Bill & Melinda Gates Foundation.
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            Exosomes

            Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. This pathway of intercellular vesicle traffic plays important roles in many aspects of human health and disease, including development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases. In addition, viruses co-opt exosome biogenesis pathways both for assembling infectious particles and for establishing host permissiveness. On the basis of these and other properties, exosomes are being developed as therapeutic agents in multiple disease models.
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              Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement

              Lung cancer is the second most common cancer and the leading cause of cancer death in the US. In 2020, an estimated 228 820 persons were diagnosed with lung cancer, and 135 720 persons died of the disease. The most important risk factor for lung cancer is smoking. Increasing age is also a risk factor for lung cancer. Lung cancer has a generally poor prognosis, with an overall 5-year survival rate of 20.5%. However, early-stage lung cancer has a better prognosis and is more amenable to treatment.
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                Author and article information

                Journal
                J Thorac Dis
                J Thorac Dis
                JTD
                Journal of Thoracic Disease
                AME Publishing Company
                2072-1439
                2077-6624
                23 May 2023
                30 May 2023
                : 15
                : 5
                : 2616-2626
                Affiliations
                [1]deptDepartment of Thoracic Surgery, Changhai Hospital , Second Military Medical University , Shanghai, China
                Author notes

                Contributions: (I) Conception and design: M Li, X Wang; (II) Administrative support: H Jin; (III) Provision of study materials or patients: T Liu; (IV) Collection and assembly of data: M Li, W Cheng; (V) Data analysis and interpretation: M Li, T Liu, X Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Xiaowei Wang, MD. Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Yangpu District, Shanghai 200433, China. Email: drwxw@ 123456163.com ; Hai Jin, MD, PhD. Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Yangpu District, Shanghai 200433, China. Email: Projinhai@ 123456163.com .
                [^]

                ORCID: 0000-0001-6500-8132.

                Article
                jtd-15-05-2616
                10.21037/jtd-23-398
                10267929
                37324093
                bdc1a717-d827-495c-bc9a-4256fca98bb7
                2023 Journal of Thoracic Disease. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 24 December 2022
                : 10 May 2023
                Categories
                Original Article

                non-small cell lung cancer (nsclc),exosomes,microrna (mirna),liquid biopsy

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