{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T01:09:34Z","timestamp":1786237774529,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Lietuvos Mokslo Taryba","doi-asserted-by":"publisher","award":["S-MIP-17-108"],"award-info":[{"award-number":["S-MIP-17-108"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients\u2019 functional\/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients\u2019 quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p &lt; 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients\u2019 quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients\u2019 functional parameters (p &lt; 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p &lt; 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients\u2019 functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b\/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.<\/jats:p>","DOI":"10.3390\/ijms21207450","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"7450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Unique Interplay between Molecular miR-181b\/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5946-1731","authenticated-orcid":false,"given":"Rytis","family":"Stakaitis","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-3504","authenticated-orcid":false,"given":"Aiste","family":"Pranckeviciene","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-6272","authenticated-orcid":false,"given":"Giedrius","family":"Steponaitis","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arimantas","family":"Tamasauskas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0446-6898","authenticated-orcid":false,"given":"Adomas","family":"Bunevicius","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Medicine, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3297-8882","authenticated-orcid":false,"given":"Paulina","family":"Vaitkiene","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1200\/JCO.2017.73.0119","article-title":"Adult Glioblastoma","volume":"35","author":"Alexander","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1093\/neuonc\/nop045","article-title":"Symptoms and problems in the end-of-life phase of high-grade glioma patients","volume":"12","author":"Sizoo","year":"2010","journal-title":"Neuro-Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11060-010-0389-0","article-title":"Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme","volume":"103","author":"Ulrich","year":"2011","journal-title":"J. Neurooncol."},{"key":"ref_4","first-page":"1","article-title":"The Evidence of Glioblastoma Heterogeneity","volume":"5","author":"Soeda","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.3390\/cancers5041306","article-title":"MicroRNA in Human Glioma","volume":"5","author":"Li","year":"2013","journal-title":"Cancers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrm3854","article-title":"Regulation of microRNA function in somatic stem cell proliferation and differentiation","volume":"15","author":"Shenoy","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10571-013-9997-5","article-title":"The Involvement of MicroRNAs in Major Depression, Suicidal Behavior, and Related Disorders: A Focus on miR-185 and miR-491-3p","volume":"34","author":"Serafini","year":"2014","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.psyneuen.2015.10.019","article-title":"MicroRNA-155 deletion reduces anxiety- and depressive-like behaviors in mice","volume":"63","author":"Fonken","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"850","DOI":"10.4161\/rna.20378","article-title":"Small RNAs have a large impact","volume":"9","author":"Weiland","year":"2012","journal-title":"RNA Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41571-018-0035-x","article-title":"Clinical utility of circulating non-coding RNAs\u2014An update","volume":"15","author":"Anfossi","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10513","DOI":"10.1073\/pnas.0804549105","article-title":"Circulating microRNAs as stable blood-based markers for cancer detection","volume":"105","author":"Mitchell","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1182\/blood-2011-11-389478","article-title":"Functional transfer of microRNA by exosomes","volume":"119","author":"Stoorvogel","year":"2012","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.compbiomed.2014.06.004","article-title":"Evolution of the mir-181 microRNA family","volume":"52","author":"Yang","year":"2014","journal-title":"Comput. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1158\/1541-7786.MCR-14-0697","article-title":"miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis","volume":"13","author":"Sun","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_15","first-page":"1","article-title":"Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma","volume":"5","author":"Wang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.bbrc.2005.07.030","article-title":"Extensive modulation of a set of microRNAs in primary glioblastoma","volume":"334","author":"Galardi","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s11764-017-0602-7","article-title":"Life beyond a diagnosis of glioblastoma: A systematic review of the literature","volume":"11","author":"Gately","year":"2017","journal-title":"J. Cancer Surviv. Res. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/neuonc\/nos089","article-title":"miR-181d: A predictive glioblastoma biomarker that downregulates MGMT expression","volume":"14","author":"Zhang","year":"2012","journal-title":"Neuro-Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rynkeviciene, R., Simiene, J., Strainiene, E., Stankevicius, V., Usinskiene, J., Kaubriene, E.M., Meskinyte, I., Cicenas, J., and Suziedelis, K. (2019). Non-Coding RNAs in Glioma. Cancers, 11.","DOI":"10.3390\/cancers11010017"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1002\/jcb.26116","article-title":"lncRNA CCAT1 Promotes Glioma Tumorigenesis by Sponging miR-181b","volume":"118","author":"Cui","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3727\/096504016X14791732531006","article-title":"MicroRNA-181b Inhibits Cellular Proliferation and Invasion of Glioma Cells via Targeting Sal-Like Protein 4","volume":"25","author":"Zhou","year":"2017","journal-title":"Oncol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s11060-009-9797-4","article-title":"miR-21 and 221 upregulation and miR-181b downregulation in human grade II\u2013IV astrocytic tumors","volume":"93","author":"Conti","year":"2009","journal-title":"J. Neurooncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1261\/rna.035972.112","article-title":"MiRNA-181b suppresses IGF-1R and functions as a tumor suppressor gene in gliomas","volume":"19","author":"Shi","year":"2013","journal-title":"RNA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ho, K.-H., Chen, P.-H., Hsi, E., Shih, C.-M., Chang, W.-C., Cheng, C.-H., Lin, C.-W., and Chen, K.-C. (2017). Identification of IGF-1-enhanced cytokine expressions targeted by miR-181d in glioblastomas via an integrative miRNA\/mRNA regulatory network analysis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-00826-0"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28195","DOI":"10.18632\/oncotarget.8618","article-title":"miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma","volume":"7","author":"Khalil","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/WNR.0000000000000302","article-title":"Tumor suppressor miR-181c attenuates proliferation, invasion, and self-renewal abilities in glioblastoma","volume":"26","author":"Ruan","year":"2015","journal-title":"NeuroReport"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/aps.2017.173","article-title":"MicroRNAs as biomarkers for human glioblastoma: Progress and potential","volume":"39","author":"Huang","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","first-page":"1","article-title":"Diagnostic value of a plasma microRNA signature in gastric cancer: A microRNA expression analysis","volume":"5","author":"Zhou","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.surneu.2008.07.016","article-title":"Association of preoperative depression and survival after resection of malignant brain astrocytoma","volume":"71","author":"Gathinji","year":"2009","journal-title":"Surg. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ejca.2019.05.012","article-title":"The added value of health-related quality of life as a prognostic indicator of overall survival and progression- free survival in glioma patients: A meta-analysis based on individual patient data from randomised controlled trials","volume":"116","author":"Coomans","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"989","DOI":"10.3171\/2015.4.JNS15194","article-title":"Quality of survival the 1st year with glioblastoma: A longitudinal study of patient-reported quality of life","volume":"124","author":"Sagberg","year":"2016","journal-title":"J. Neurosurg."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jakola, A.S., Gulati, S., Weber, C., Unsga, G., and Solheim, O. (2011). Postoperative Deterioration in Health Related Quality of Life as Predictor for Survival in Patients with Glioblastoma: A Prospective Study. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028592"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11136-011-9932-5","article-title":"Circulating levels of a biomarker of collagen metabolism are associated with health-related quality of life in patients with chronic heart failure","volume":"21","author":"Chatzikyriakou","year":"2012","journal-title":"Qual. Life Res."},{"key":"ref_34","first-page":"A7145","article-title":"Health Related Quality of Life and Biomarker Levels in Patients with Idiopathic Pulmonary Fibrosis","volume":"199","author":"Kay","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/jnc.12662","article-title":"Serum miR-206 and other muscle-specific microRNAs as non-invasive biomarkers for Duchenne muscular dystrophy","volume":"129","author":"Hu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vaitkiene, P., Pranckeviciene, A., Stakaitis, R., Steponaitis, G., Tamasauskas, A., and Bunevicius, A. (2019). Association of miR-34a Expression with Quality of Life of Glioblastoma Patients: A Prospective Study. Cancers, 11.","DOI":"10.3390\/cancers11030300"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s11060-016-2311-x","article-title":"Association of thyroid hormone concentrations with quality of life of primary brain tumor patients: A pilot study","volume":"131","author":"Bunevicius","year":"2017","journal-title":"J. Neurooncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/B978-0-12-802997-8.00016-5","article-title":"Epilepsy and brain tumors","volume":"134","author":"Englot","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"ref_39","first-page":"1","article-title":"Deep Learning based Radiomics (DLR) and its usage in noninvasive IDH1 prediction for low grade glioma","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1093\/neuonc\/nou104","article-title":"Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria","volume":"17","author":"Jansen","year":"2015","journal-title":"Neuro-Oncol."},{"key":"ref_41","unstructured":"Fayers, P., Aaronson, N.K., Bjordal, K., Groenvold, M., Curran, D., and Bottomley, A. (2001). EORTC QLQ-C30 Scoring Manual, European Organisation for Research and Treatment of Cancer."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Husson, O., de Rooij, B.H., Kieffer, J., Oerlemans, S., Mols, F., Aaronson, N.K., van der Graaf, W.T.A., and van de Poll-Franse, L.V. (2019). The EORTC QLQ-C30 Summary Score as Prognostic Factor for Survival of Patients with Cancer in the \u201cReal-World\u201d: Results from the Population-Based PROFILES Registry. Oncologist.","DOI":"10.1634\/theoncologist.2019-0348"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.jval.2019.06.004","article-title":"Validation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Summary Score in Patients With Hematologic Malignancies","volume":"22","author":"Efficace","year":"2019","journal-title":"Value Health J. Int. Soc. Pharmacoeconomics Outcomes Res."},{"key":"ref_44","first-page":"1033","article-title":"An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients","volume":"46","author":"Taphoorn","year":"2010","journal-title":"Eur. J. Cancer Oxf. Engl. 1990"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1002\/1097-0142(19840501)53:9<2002::AID-CNCR2820530933>3.0.CO;2-W","article-title":"The Karnofsky Performance Status Scale. An examination of its reliability and validity in a research setting","volume":"53","author":"Mor","year":"1984","journal-title":"Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:18:02Z","timestamp":1760177882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/20\/7450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,9]]},"references-count":45,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21207450"],"URL":"https:\/\/doi.org\/10.3390\/ijms21207450","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,9]]}}}