{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:21:55Z","timestamp":1783488115841,"version":"3.55.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"crossref","award":["FONDO SECTORIAL SALUD-2012-01-181492"],"award-info":[{"award-number":["FONDO SECTORIAL SALUD-2012-01-181492"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01DN15002"],"award-info":[{"award-number":["01DN15002"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondo de Investigaci\u00f3n de Salud","award":["FIS-IMSS-G11-935"],"award-info":[{"award-number":["FIS-IMSS-G11-935"]}]},{"DOI":"10.13039\/501100006254","name":"Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006254","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007709","name":"Fondo de Cooperaci\u00f3n Internacional en Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["207978"],"award-info":[{"award-number":["207978"]}],"id":[{"id":"10.13039\/501100007709","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney<jats:italic>U<\/jats:italic>test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants \u226460 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.<\/jats:p>","DOI":"10.1371\/journal.pone.0275936","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T18:21:36Z","timestamp":1665771696000},"page":"e0275936","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Assessment of miR-103a-3p in leukocytes\u2014No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis"],"prefix":"10.1371","volume":"17","author":[{"given":"Carmina","family":"Jim\u00e9nez-Ram\u00edrez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9009-8387","authenticated-orcid":true,"given":"Daniel","family":"Gilbert Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Aguilar-Madrid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Brik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuauht\u00e9moc Arturo","family":"Ju\u00e1rez-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-8859","authenticated-orcid":true,"given":"Swaantje","family":"Casjens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Raiko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-5946","authenticated-orcid":true,"given":"Georg","family":"Johnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9175-5617","authenticated-orcid":true,"given":"Alejandro","family":"Cabello-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"pone.0275936.ref001","unstructured":"IARC monographs on the evaluation of the carcinogenic risk of chemicals to man: asbestos. 1977\/01\/01 ed1977. 1\u2013106 p."},{"key":"pone.0275936.ref002","unstructured":"Secretary IBA. Current asbestos ban 2019."},{"issue":"2","key":"pone.0275936.ref003","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jtho.2015.11.005","article-title":"The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification","volume":"11","author":"F Galateau-Salle","year":"2016","journal-title":"J Thorac Oncol."},{"issue":"1","key":"pone.0275936.ref004","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5858\/arpa.2017-0124-RA","article-title":"Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group","volume":"142","author":"AN Husain","year":"2018","journal-title":"Archives of pathology & laboratory medicine"},{"issue":"10272","key":"pone.0275936.ref005","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial","volume":"397","author":"P Baas","year":"2021","journal-title":"Lancet"},{"issue":"5","key":"pone.0275936.ref006","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00408-019-00244-1","article-title":"Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma","volume":"197","author":"C Jimenez-Ramirez","year":"2019","journal-title":"Lung"},{"issue":"3","key":"pone.0275936.ref007","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.lungcan.2015.09.021","article-title":"Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma","volume":"90","author":"L Santarelli","year":"2015","journal-title":"Lung Cancer"},{"issue":"1","key":"pone.0275936.ref008","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/s12885-017-3375-5","article-title":"Calretinin as a blood-based biomarker for mesothelioma","volume":"17","author":"G Johnen","year":"2017","journal-title":"BMC cancer"},{"issue":"9","key":"pone.0275936.ref009","doi-asserted-by":"crossref","first-page":"883","DOI":"10.7150\/ijms.23939","article-title":"Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population","volume":"15","author":"G Aguilar-Madrid","year":"2018","journal-title":"International journal of medical sciences"},{"issue":"6","key":"pone.0275936.ref010","doi-asserted-by":"crossref","DOI":"10.3390\/cancers10060203","article-title":"Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on","volume":"10","author":"C Ledda","year":"2018","journal-title":"Cancers (Basel)"},{"issue":"11","key":"pone.0275936.ref011","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1093\/carcin\/bgz103","article-title":"Biomarkers for malignant pleural mesothelioma: a meta-analysis","volume":"40","author":"CN Gillezeau","year":"2019","journal-title":"Carcinogenesis"},{"issue":"Suppl 2","key":"pone.0275936.ref012","doi-asserted-by":"crossref","first-page":"S353","DOI":"10.21037\/jtd.2017.10.132","article-title":"Serum mesothelin and other biomarkers: what have we learned in the last decade?","volume":"10","author":"A Cristaudo","year":"2018","journal-title":"J Thorac Dis"},{"key":"pone.0275936.ref013","doi-asserted-by":"crossref","first-page":"e004145","DOI":"10.1136\/bmjopen-2013-004145","article-title":"Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis","volume":"4","author":"A Cui","year":"2014","journal-title":"BMJ open"},{"issue":"11","key":"pone.0275936.ref014","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1158\/0008-5472.CAN-14-0337","article-title":"Discovery of mesothelin and exploiting it as a target for immunotherapy","volume":"74","author":"I Pastan","year":"2014","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0275936.ref015","doi-asserted-by":"crossref","first-page":"14321","DOI":"10.1038\/s41598-018-32315-3","article-title":"Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin\u2014a case-control comparison nested into a prospective cohort of asbestos-exposed workers","volume":"8","author":"G Johnen","year":"2018","journal-title":"Sci Rep"},{"issue":"36","key":"pone.0275936.ref016","doi-asserted-by":"crossref","first-page":"58606","DOI":"10.18632\/oncotarget.9686","article-title":"Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis","volume":"7","author":"L Micolucci","year":"2016","journal-title":"Oncotarget"},{"issue":"2","key":"pone.0275936.ref017","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/apha.12681","article-title":"MicroRNAs in metabolism","volume":"219","author":"S Vienberg","year":"2017","journal-title":"Acta Physiol (Oxf)"},{"key":"pone.0275936.ref018","doi-asserted-by":"crossref","first-page":"9645940","DOI":"10.1155\/2017\/9645940","article-title":"MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study","volume":"2017","author":"P Mozzoni","year":"2017","journal-title":"Dis Markers"},{"issue":"1","key":"pone.0275936.ref019","doi-asserted-by":"crossref","first-page":"e30221","DOI":"10.1371\/journal.pone.0030221","article-title":"Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma\u2014a pilot study","volume":"7","author":"DG Weber","year":"2012","journal-title":"PLoS One"},{"key":"pone.0275936.ref020","doi-asserted-by":"crossref","first-page":"9280170","DOI":"10.1155\/2017\/9280170","article-title":"Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma","volume":"2017","author":"DG Weber","year":"2017","journal-title":"Dis Markers"},{"issue":"7","key":"pone.0275936.ref021","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/JTO.0b013e3182572e83","article-title":"Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma","volume":"7","author":"MB Kirschner","year":"2012","journal-title":"J Thorac Oncol"},{"issue":"2","key":"pone.0275936.ref022","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2217\/bmm-2017-0224","article-title":"Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients","volume":"12","author":"M Matboli","year":"2018","journal-title":"Biomark Med"},{"issue":"50","key":"pone.0275936.ref023","doi-asserted-by":"crossref","first-page":"82700","DOI":"10.18632\/oncotarget.12408","article-title":"Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers","volume":"7","author":"I Bononi","year":"2016","journal-title":"Oncotarget"},{"key":"pone.0275936.ref024","doi-asserted-by":"crossref","first-page":"650","DOI":"10.3389\/fonc.2018.00650","article-title":"MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review","volume":"8","author":"G Lo Russo","year":"2018","journal-title":"Front Oncol."},{"issue":"12","key":"pone.0275936.ref025","doi-asserted-by":"crossref","first-page":"e114483","DOI":"10.1371\/journal.pone.0114483","article-title":"Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis","volume":"9","author":"DG Weber","year":"2014","journal-title":"PLoS One"},{"key":"pone.0275936.ref026","first-page":"272","article-title":"Globalization and the transfer of hazardous industry: asbestos in Mexico, 1979\u20132000","volume":"2003","author":"G Aguilar-Madrid","journal-title":"International journal of occupational and environmental health"},{"key":"pone.0275936.ref027","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ajim.20780","article-title":"Case-control study of pleural mesothelioma in workers with social security in Mexico","volume":"53","author":"G Aguilar-Madrid","year":"2010","journal-title":"American journal of industrial medicine"},{"issue":"1","key":"pone.0275936.ref028","doi-asserted-by":"crossref","first-page":"e0227648","DOI":"10.1371\/journal.pone.0227648","article-title":"Impact of long-term storage and freeze-thawing on eight circulating microRNAs in plasma samples","volume":"15","author":"PR Matias-Garcia","year":"2020","journal-title":"PLoS One"},{"issue":"4","key":"pone.0275936.ref029","doi-asserted-by":"crossref","first-page":"e18232","DOI":"10.1371\/journal.pone.0018232","article-title":"Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma","volume":"6","author":"L Santarelli","year":"2011","journal-title":"PLoS One"},{"key":"pone.0275936.ref030","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/bs.pmbts.2016.12.013","article-title":"MicroRNAs as Peripheral Biomarkers in Aging and Age-Related Diseases","volume":"146","author":"S Kumar","year":"2017","journal-title":"Prog Mol Biol Transl Sci"},{"issue":"12","key":"pone.0275936.ref031","doi-asserted-by":"crossref","first-page":"E2271","DOI":"10.1210\/jc.2012-1996","article-title":"Circulating miRNA Profiles in Patients with Metabolic Syndrome","volume":"97","author":"DS Karolina","year":"2012","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"issue":"1","key":"pone.0275936.ref032","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1038\/s41467-019-10116-0","article-title":"Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK\/NF-\u03baB\/p65 regulatory axis","volume":"10","author":"Q Lu","year":"2019","journal-title":"Nature Communications"},{"issue":"2","key":"pone.0275936.ref033","doi-asserted-by":"crossref","first-page":"e039079","DOI":"10.1136\/bmjopen-2020-039079","article-title":"Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine","volume":"11","author":"S Casjens","year":"2021","journal-title":"BMJ Open"},{"key":"pone.0275936.ref034","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.diabres.2018.03.044","article-title":"MicroRNA expression profile in plasma from type 1 diabetic patients: Case-control study and bioinformatic analysis","volume":"141","author":"TS Assmann","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"issue":"3","key":"pone.0275936.ref035","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00592-019-01430-6","article-title":"Circulating miR-103 family as potential biomarkers for type 2 diabetes through targeting CAV-1 and SFRP4","volume":"57","author":"M Luo","year":"2020","journal-title":"Acta Diabetol."},{"key":"pone.0275936.ref036","unstructured":"National Institute of Statistics and Geography. Press release 645\/21. 12 November 2021. Available at https:\/\/www.inegi.org.mx\/contenidos\/saladeprensa\/aproposito\/2021\/EAP_Diabetes2021.pdf."},{"issue":"1","key":"pone.0275936.ref037","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1038\/s41467-019-10116-0","article-title":"Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK\/NF-\u03baB\/p65 regulatory axis","volume":"10","author":"Q Lu","year":"2019","journal-title":"Nat Commun."},{"issue":"12","key":"pone.0275936.ref038","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1080\/15592294.2020.1780081","article-title":"Age-related epigenetic drift deregulates SIRT6 expression and affects its downstream genes in human peripheral blood mononuclear cells","volume":"15","author":"M Owczarz","year":"2020","journal-title":"Epigenetics"},{"issue":"5","key":"pone.0275936.ref039","doi-asserted-by":"crossref","first-page":"e0176680","DOI":"10.1371\/journal.pone.0176680","article-title":"Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease","volume":"12","author":"T Cavalleri","year":"2017","journal-title":"PLoS One"},{"issue":"10","key":"pone.0275936.ref040","doi-asserted-by":"crossref","DOI":"10.3390\/jpm11101014","article-title":"Extracellular Vesicle Enriched miR-625-3p Is Associated with Survival of Malignant Mesothelioma Patients","volume":"11","author":"K Gori\u010dar","year":"2021","journal-title":"J Pers Med."},{"key":"pone.0275936.ref041","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.gene.2018.11.055","article-title":"A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis","volume":"687","author":"H Zhang","year":"2019","journal-title":"Gene"},{"issue":"1","key":"pone.0275936.ref042","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3892\/ol.2021.13156","article-title":"Circulating microRNA-103a-3p could be a diagnostic and prognostic biomarker for breast cancer","volume":"23","author":"H Liu","year":"2022","journal-title":"Oncol Lett"},{"issue":"2","key":"pone.0275936.ref043","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/carcin\/bgy167","article-title":"Circulating microRNAs combined with PSA for accurate and non-invasive prostate cancer detection","volume":"40","author":"M Mello-Grand","year":"2019","journal-title":"Carcinogenesis"},{"issue":"6","key":"pone.0275936.ref044","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.fertnstert.2020.01.026","article-title":"Identification of candidate microRNA markers of endometriosis with the use of next-generation sequencing and quantitative real-time polymerase chain reaction","volume":"113","author":"E Papari","year":"2020","journal-title":"Fertil Steril"},{"issue":"4","key":"pone.0275936.ref045","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00296-014-3139-3","article-title":"Profile of circulating microRNAs in fibromyalgia and their relation to symptom severity: an exploratory study","volume":"35","author":"JL Bjersing","year":"2015","journal-title":"Rheumatol Int."},{"issue":"1","key":"pone.0275936.ref046","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13104-019-4113-7","article-title":"Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study","volume":"12","author":"DG Weber","year":"2019","journal-title":"BMC Res Notes"},{"issue":"4","key":"pone.0275936.ref047","doi-asserted-by":"crossref","first-page":"535","DOI":"10.18388\/abp.2011_2221","article-title":"How the RNA isolation method can affect microRNA microarray results","volume":"58","author":"A Podolska","year":"2011","journal-title":"Acta Biochim Pol"},{"issue":"7","key":"pone.0275936.ref048","doi-asserted-by":"crossref","first-page":"e0220406","DOI":"10.1371\/journal.pone.0220406","article-title":"Variance component analysis of circulating miR-122 in serum from healthy human volunteers","volume":"14","author":"J Vogt","year":"2019","journal-title":"PLoS One"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0275936","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T22:39:20Z","timestamp":1701211160000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0275936"}},"subtitle":[],"editor":[{"given":"Stefania","family":"Crispi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0275936","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,14]]}}}