{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:52Z","timestamp":1785410572212,"version":"3.56.0"},"reference-count":89,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cInitiative Krebsforschung\u201d of the Medical University of Vienna"},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["FWF No. T 1062-B33"],"award-info":[{"award-number":["FWF No. T 1062-B33"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FWF No. T 1062-B33"],"award-info":[{"award-number":["FWF No. T 1062-B33"]}],"id":[{"id":"https:\/\/ror.org\/013tf3c58","id-type":"ROR","asserted-by":"publisher"}]},{"name":"City of Vienna Fund for Innovative Interdisciplinary Cancer Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objective: The identification of novel non-invasive diagnostic and prognostic biomarkers is urgently needed in pleural mesothelioma (PM). While soluble mesothelin-related peptides (SMRP) are the most established circulating biomarker, their prognostic value is limited. A wide range of microRNAs (miRs) play diverse roles in regulating gene expression in PM. MiR-21 has been shown to be upregulated in mesothelioma tissue; nevertheless, the diagnostic and prognostic utility of miR-21 in the circulation and its association with survival in PM have not been extensively investigated to date. The objective of the current study was to evaluate miR-21 as a potential blood-based diagnostic and prognostic biomarker in PM. Methods: Plasma samples from PM patients (n = 94) were collected at the time of diagnosis, prior to treatment. Sex- and age-matched healthy individuals (n = 30) served as controls. MiR-21 levels were measured using quantitative RT-PCR and normalized to miR-16, and potential correlations with clinicopathological data were analyzed. Serum SMRP levels were measured in matched patients (n = 84), and a direct comparative analysis of miR-21 and SMRP was conducted. In situ hybridization (ISH) was used to confirm the presence of miR-21 in tumor cells. Results: Plasma miR-21 levels were significantly elevated in PM patients compared to healthy controls (p &lt; 0.001), demonstrating good diagnostic performance (AUC 0.81). The localization of miR-21 in PM cells was confirmed by ISH. High miR-21 levels were associated with significantly shorter median overall survival (12.4 vs. 24.3 months, p &lt; 0.001). Elevated SMRP levels were also associated with reduced survival (12.4 vs. 19.5 months, p = 0.032); however, SMRP did not retain independent prognostic significance in multivariable analysis. In contrast, high-circulating miR-21 was confirmed as an independent predictor for poor survival (HR 3.12, p &lt; 0.001). Conclusions: Our findings highlight that circulating miR-21 is a potential non-invasive biomarker with both diagnostic and independent prognostic value in pleural mesothelioma and outperforms SMRP in multivariable survival analysis. Further research is warranted to validate its role in the biology of this disease and to assess its correlation with outcome and treatment responses.<\/jats:p>","DOI":"10.3390\/diagnostics16081142","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:29:29Z","timestamp":1776065369000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MiR-21 Is a Novel Diagnostic and Prognostic Circulating Biomarker in Pleural Mesothelioma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9805-9733","authenticated-orcid":false,"given":"Berta","family":"Mosleh","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-1228","authenticated-orcid":false,"given":"Yawen","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Lang","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Klikovits","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Thoracic Surgery, Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Sinn","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kao","sequence":"additional","affiliation":[{"name":"Sydney Medical School, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Jakopovic","sequence":"additional","affiliation":[{"name":"Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb,  School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-991X","authenticated-orcid":false,"given":"Clemens","family":"Aigner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-4153","authenticated-orcid":false,"given":"Balazs","family":"Heged\u00fcs","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Medicine Essen, University Duisburg-Essen, 45239 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8719-2206","authenticated-orcid":false,"given":"Natalie","family":"Baldes","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Medicine Essen, University Duisburg-Essen, 45239 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8275-5957","authenticated-orcid":false,"given":"Servet","family":"B\u00f6l\u00fckbas","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Medicine Essen, University Duisburg-Essen, 45239 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-8624","authenticated-orcid":false,"given":"Balazs","family":"Dome","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"National Koranyi Institute of Pulmonology, 1121 Budapest, Hungary"},{"name":"Department of Thoracic Surgery, National Institute of Oncology, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-8768","authenticated-orcid":false,"given":"Mir Alireza","family":"Hoda","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Laszlo","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-9340","authenticated-orcid":false,"given":"Michael","family":"Grusch","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schelch","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Center for Cancer Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.jtho.2024.08.022","article-title":"The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma","volume":"19","author":"Kindler","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cllc.2025.04.008","article-title":"Breaking Through: Immunotherapy Innovations in Pleural Mesothelioma","volume":"26","author":"Sofianidi","year":"2025","journal-title":"Clin. Lung Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Strbac, D., and Dolzan, V. (2022). Novel and Future Treatment Options in Mesothelioma: A Systematic Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23041975"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Suraya, R., Nagano, T., and Tachihara, M. (2025). Recent Advances in Mesothelioma Treatment: Immunotherapy, Advanced Cell Therapy, and Other Innovative Therapeutic Modalities. Cancers, 17.","DOI":"10.3390\/cancers17040694"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1200\/JCO-24-02425","article-title":"Treatment of Pleural Mesothelioma: ASCO Guideline Update","volume":"43","author":"Kindler","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/CCO.0000000000000697","article-title":"Malignant pleural mesothelioma: Recent developments","volume":"33","author":"Sinn","year":"2021","journal-title":"Curr. Opin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/S0140-6736(03)14794-0","article-title":"Mesothelin-family proteins and diagnosis of mesothelioma","volume":"362","author":"Robinson","year":"2003","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1200\/JCO.2011.39.6671","article-title":"Serum mesothelin for diagnosing malignant pleural mesothelioma: An individual patient data meta-analysis","volume":"30","author":"Hollevoet","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Johnen, G., Gawrych, K., Raiko, I., Casjens, S., Pesch, B., Weber, D.G., Taeger, D., Lehnert, M., Kollmeier, J., and Bauer, T. (2017). Calretinin as a blood-based biomarker for mesothelioma. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3375-5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"434","DOI":"10.37349\/etat.2020.00028","article-title":"Circulating biomarkers in malignant pleural mesothelioma","volume":"1","author":"Viscardi","year":"2020","journal-title":"Explor. Target. Antitumor Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sorino, C., Mondoni, M., Marchetti, G., Agati, S., Inchingolo, R., Mei, F., Flamini, S., Lococo, F., and Feller-Kopman, D. (2023). Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers. J. Clin. Med., 12.","DOI":"10.3390\/jcm12227006"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1373\/clinchem.2006.079327","article-title":"MESOMARK: A potential test for malignant pleural mesothelioma","volume":"53","author":"Beyer","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Grosso, F., Mannucci, M., Ugo, F., Ferro, P., Cassinari, M., Vigani, A., De Angelis, A.M., Delfanti, S., Lia, M., and Guaschino, R. (2021). Pilot Study to Evaluate Serum Soluble Mesothelin-Related Peptide (SMRP) as Marker for Clinical Monitoring of Pleural Mesothelioma (PM): Correlation with Modified RECIST Score. Diagnostics, 11.","DOI":"10.3390\/diagnostics11112015"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1016\/j.athoracsur.2017.06.042","article-title":"Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma","volume":"104","author":"Burt","year":"2017","journal-title":"Ann. Thorac. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/bjc.2017.22","article-title":"Prognostication and monitoring of mesothelioma using biomarkers: A systematic review","volume":"116","author":"Arnold","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15004","DOI":"10.1038\/sigtrans.2015.4","article-title":"The role of MicroRNAs in human cancer","volume":"1","author":"Peng","year":"2016","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","first-page":"1","article-title":"Determining The Role of MicroRNAs in Self-Renewal, Metastasis and Resistance to Drugs in Human Gastric Cancer Based on Data Mining Approaches: A Systematic Review","volume":"24","author":"Azimi","year":"2022","journal-title":"Cell J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8309015","DOI":"10.1155\/2018\/8309015","article-title":"Prognostic Role of MicroRNAs in Human Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis","volume":"2018","author":"Lamichhane","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"882","DOI":"10.2174\/1566524022666211217114527","article-title":"Role of MicroRNAs and Long Non-Coding RNAs in Regulating Angiogenesis in Human Breast Cancer: A Molecular Medicine Perspective","volume":"22","author":"Golhani","year":"2022","journal-title":"Curr. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12957-025-03732-2","article-title":"An update on the molecular mechanisms underlying the progression of miR-21 in oral cancer","volume":"23","author":"Prasad","year":"2025","journal-title":"World J. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1038\/s41598-017-02694-0","article-title":"Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism","volume":"7","author":"Melaiu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lo Russo, G., Tessari, A., Capece, M., Galli, G., de Braud, F., Garassino, M.C., and Palmieri, D. (2018). MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00650"},{"key":"ref_23","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":"Mozzoni","year":"2017","journal-title":"Dis. Markers"},{"key":"ref_24","first-page":"1031","article-title":"MicroRNAs in mesothelioma: From tumour suppressors and biomarkers to therapeutic targets","volume":"7","author":"Reid","year":"2015","journal-title":"J. Thorac. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.20517\/2394-4722.2022.70","article-title":"Promising therapeutic potential of tumor suppressor microRNAs for malignant pleural mesothelioma","volume":"8","author":"Dixit","year":"2022","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Reid, G., Johnson, T.G., and van Zandwijk, N. (2020). Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00105"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1097\/JTO.0b013e31820db125","article-title":"MicroRNAs dysregulation in human malignant pleural mesothelioma","volume":"6","author":"Balatti","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106568","DOI":"10.1016\/j.phrs.2022.106568","article-title":"Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents","volume":"187","author":"Hashemi","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.omtn.2020.03.003","article-title":"The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics","volume":"20","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3892\/br.2016.747","article-title":"Emerging role of microRNA-21 in cancer","volume":"5","author":"Feng","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sheedy, F.J. (2015). Turning 21: Induction of miR-21 as a Key Switch in the Inflammatory Response. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00019"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.1172\/JCI127125","article-title":"Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response","volume":"129","author":"Sahraei","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, S., Wan, X., and Ruan, Q. (2016). The MicroRNA-21 in Autoimmune Diseases. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060864"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10184","DOI":"10.3389\/ti.2021.10184","article-title":"MiR-21 in Lung Transplant Recipients With Chronic Lung Allograft Dysfunction","volume":"35","author":"Miyahara","year":"2021","journal-title":"Transpl. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/j.jtho.2016.09.124","article-title":"The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma","volume":"11","author":"Rusch","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/j.jtho.2016.09.121","article-title":"The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma","volume":"11","author":"Rice","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1016\/j.jtho.2016.08.147","article-title":"The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma","volume":"11","author":"Nowak","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/j.jtho.2016.09.123","article-title":"The IASLC Mesothelioma Staging Project: Improving Staging of a Rare Disease Through International Participation","volume":"11","author":"Pass","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kirschner, M.B., van Zandwijk, N., and Reid, G. (2013). Cell-free microRNAs: Potential biomarkers in need of standardized reporting. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00056"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1038\/s41416-023-02219-9","article-title":"Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer","volume":"128","author":"Valko","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ymeth.2010.07.002","article-title":"Robust one-day in situ hybridization protocol for detection of microRNAs in paraffin samples using LNA probes","volume":"52","author":"Jorgensen","year":"2010","journal-title":"Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e1627","DOI":"10.1002\/wrna.1627","article-title":"microRNA strand selection: Unwinding the rules","volume":"12","author":"Medley","year":"2021","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/s41598-017-01904-z","article-title":"Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: Evidence from comprehensive miRNA expression profiling analysis and clinical validation","volume":"7","author":"Qu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.21873\/cgp.20090","article-title":"Pre-operative Plasma miR-21-5p Is a Sensitive Biomarker and Independent Prognostic Factor in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Resection","volume":"15","author":"Karasek","year":"2018","journal-title":"Cancer Genom. Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1007\/s10143-025-03747-z","article-title":"Determination of longitudinal Circulating levels of miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients with glioblastoma using droplet digital PCR","volume":"48","author":"Donofrio","year":"2025","journal-title":"Neurosurg. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Burlacu, I., Aschie, M., Cozaru, G.C., Deacu, M., Vizireanu, G.M., Mitroi, A.N., Mitroi, A.F., and Brinzan, C.S. (2025). The miR-21-5p, miR-30c-5p, and miR-182-5p as Biomarkers in Clear Cell Renal Cell Carcinoma: A Southeastern Romanian Cohort Study. Genes, 16.","DOI":"10.3390\/genes16060650"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"210057","DOI":"10.1183\/16000617.0057-2021","article-title":"Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: A systematic review and meta-analysis","volume":"30","author":"Schillebeeckx","year":"2021","journal-title":"Eur. Respir. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"244","DOI":"10.21037\/atm.2017.06.60","article-title":"Diagnosis and prognosis-review of biomarkers for mesothelioma","volume":"5","author":"Sun","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rhim, J., Baek, W., Seo, Y., and Kim, J.H. (2022). From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells, 11.","DOI":"10.3390\/cells11182791"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1007\/s11605-008-0584-x","article-title":"MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival","volume":"12","author":"Dillhoff","year":"2008","journal-title":"J. Gastrointest. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4048\/jbc.2011.14.4.269","article-title":"Prognostic Implications of MicroRNA-21 Overexpression in Invasive Ductal Carcinomas of the Breast","volume":"14","author":"Lee","year":"2011","journal-title":"J. Breast Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"121340","DOI":"10.1016\/j.lfs.2022.121340","article-title":"The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review","volume":"316","author":"Vakili","year":"2023","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.molonc.2014.11.007","article-title":"MiR-score: A novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma","volume":"9","author":"Kirschner","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17300","DOI":"10.18632\/oncotarget.24644","article-title":"MiR-21 over-expression and Programmed Cell Death 4 down-regulation features malignant pleural mesothelioma","volume":"9","author":"Nicole","year":"2018","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/cncy.21646","article-title":"Young investigator challenge: MicroRNA-21\/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology","volume":"124","author":"Cappellesso","year":"2016","journal-title":"Cancer Cytopathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3233\/CBM-210090","article-title":"Assessment of a panel of miRNAs in serum and pleural fluid for the differential diagnosis of malignant and benign pleural effusion","volume":"33","author":"Zhu","year":"2022","journal-title":"Cancer Biomark."},{"key":"ref_57","first-page":"7362","article-title":"Upregulation of circulating miR-21 is associated with poor prognosis of nasopharyngeal carcinoma","volume":"10","author":"He","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gkioka, A.I., Tsota, M., Koudouna, A., Gkiokas, A., Mitropoulou, C.A., Palaiokrassa, A., Alexandropoulos, A., Papadatou-Gigante, M., Bartzi, V., and Tryfou, T.M. (2024). Circulating miR-16 and miR-21 Levels in Multiple Myeloma: Prognostic Significance of Survival and Response to Lenalidomide Treatment. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202404.1056.v1"},{"key":"ref_59","first-page":"873","article-title":"Prognostic value of circulating microRNA-21 in digestive system cancers: A meta-analysis","volume":"7","author":"Ye","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"68894","DOI":"10.18632\/oncotarget.12028","article-title":"Diagnostic value of circulating miR-21: An update meta-analysis in various cancers and validation in endometrial cancer","volume":"7","author":"Gao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"O100","DOI":"10.1111\/codi.12917","article-title":"The accuracy of circulating microRNA-21 in the diagnosis of colorectal cancer: A systematic review and meta-analysis","volume":"17","author":"Xu","year":"2015","journal-title":"Colorectal Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1038\/sj.onc.1210856","article-title":"MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer","volume":"27","author":"Asangani","year":"2008","journal-title":"Oncogene"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"20616","DOI":"10.1038\/srep20616","article-title":"Colorectal cancer characterization and therapeutic target prediction based on microRNA expression profile","volume":"6","author":"Xu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1158\/1055-9965.EPI-14-0598","article-title":"Diagnostic and prognostic value of microRNA-21 in colorectal cancer: An original study and individual participant data meta-analysis","volume":"23","author":"Zhang","year":"2014","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s00432-012-1244-9","article-title":"The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors","volume":"138","author":"Wang","year":"2012","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5298","DOI":"10.1038\/s41598-021-84707-7","article-title":"Circulating miR-21, miR-29a, and miR-126 are associated with premature death risk due to cancer and cardiovascular disease: The JACC Study","volume":"11","author":"Yamada","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"490","DOI":"10.7150\/jca.12351","article-title":"Evaluation of Plasma miR-21 and miR-152 as Diagnostic Biomarkers for Common Types of Human Cancers","volume":"7","author":"Chen","year":"2016","journal-title":"J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.31557\/APJCP.2019.20.4.1223","article-title":"Upregulation of Circulating MiR-21 Expression as a Potential Biomarker for Therapeutic Monitoring and Clinical Outcome in Breast Cancer","volume":"20","author":"Anwar","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41389-022-00413-7","article-title":"MicroRNA-21 is immunosuppressive and pro-metastatic via separate mechanisms","volume":"11","author":"Chi","year":"2022","journal-title":"Oncogenesis"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21691401.2016.1216856","article-title":"Prognostic value of circulating microRNA-21 for breast cancer: A systematic review and meta-analysis","volume":"45","author":"Jinling","year":"2017","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.2147\/OTT.S232876","article-title":"Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts","volume":"13","author":"Zhao","year":"2020","journal-title":"Onco Targets Ther."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Pop-Bica, C., Pintea, S., Magdo, L., Cojocneanu, R., Gulei, D., Ferracin, M., and Berindan-Neagoe, I. (2020). The Clinical Utility of miR-21 and let-7 in Non-small Cell Lung Cancer (NSCLC). A Systematic Review and Meta-Analysis. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.516850"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"BSR20211653","DOI":"10.1042\/BSR20211653","article-title":"MicroRNA-21 as a diagnostic and prognostic biomarker of lung cancer: A systematic review and meta-analysis","volume":"42","author":"Wang","year":"2022","journal-title":"Biosci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1007\/s11033-021-06302-3","article-title":"Circulating miR-21-5p and miR-126-3p: Diagnostic, prognostic value, and multivariate analysis in non-small-cell lung cancer","volume":"48","author":"Soliman","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"669","DOI":"10.3892\/ol.2016.5462","article-title":"Plasma miR-145, miR-20a, miR-21 and miR-223 as novel biomarkers for screening early-stage non-small cell lung cancer","volume":"13","author":"Zhang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"155601","DOI":"10.1016\/j.prp.2024.155601","article-title":"miRNA-21, an oncomiR that regulates cell proliferation, migration, invasion and therapy response in lung cancer","volume":"263","author":"Vasconcelos","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1158\/1078-0432.CCR-14-2793","article-title":"Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia","volume":"21","author":"Yamada","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3233\/CBM-140437","article-title":"Diagnostic value of circulating miR-21 for colorectal cancer: A meta-analysis","volume":"15","author":"Shan","year":"2015","journal-title":"Cancer Biomark."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4161\/epi.26842","article-title":"Epigenetic regulation of miR-21 in colorectal cancer: ITGB4 as a novel miR-21 target and a three-gene network (miR-21-ITGBeta4-PDCD4) as predictor of metastatic tumor potential","volume":"9","author":"Ferraro","year":"2014","journal-title":"Epigenetics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/07853890.2020.1828617","article-title":"Diagnostic role of circulating MiR-21 in colorectal cancer: A update meta-analysis","volume":"53","author":"Liu","year":"2021","journal-title":"Ann. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3892\/mco.2015.702","article-title":"Circulating microRNA-21 as a potential diagnostic marker for colorectal cancer: A meta-analysis","volume":"4","author":"Yu","year":"2016","journal-title":"Mol. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3892\/ijo.2014.2743","article-title":"Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer","volume":"46","author":"Abue","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Li, X., Gao, P., Wang, Y., and Wang, X. (2018). Blood-Derived microRNAs for Pancreatic Cancer Diagnosis: A Narrative Review and Meta-Analysis. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00685"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ferrari, L., Carugno, M., Mensi, C., and Pesatori, A.C. (2020). Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00445"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Cavallari, I., Urso, L., Sharova, E., Pasello, G., and Ciminale, V. (2019). Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00740"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1016\/j.cllc.2019.10.013","article-title":"Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy","volume":"21","author":"Paajanen","year":"2020","journal-title":"Clin. Lung Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ejca.2016.04.018","article-title":"Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma\u2014A multi-institutional study","volume":"63","author":"Hoda","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/bjc.2013.815","article-title":"Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma","volume":"110","author":"Ghanim","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"16456","DOI":"10.1038\/s41598-017-16551-7","article-title":"Circulating complement component 4d (C4d) correlates with tumor volume, chemotherapeutic response and survival in patients with malignant pleural mesothelioma","volume":"7","author":"Klikovits","year":"2017","journal-title":"Sci. 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