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Despite good curability with cisplatin (CDDP)-based chemotherapy, about 10% of TGCTs are non-responsive and show a chemoresistant phenotype. To further increase TGCT curability, better prediction of risk of relapse and early detection of refractory cases is needed. Therefore, to diagnose this malignancy more precisely, stratify patients more accurately and improve decision-making on treatment modality, new biomarkers are still required. Numerous studies showed association of differential expressions of microRNAs (miRNAs) with cancer. Using microarray analysis followed by RT-qPCR validation, we identified specific miRNA expression patterns that discriminate chemoresistant phenotypes in TGCTs. Comparing CDDP-resistant vs. -sensitive TGCT cell lines, we identified miR-218-5p, miR-31-5p, miR-125b-5p, miR-27b-3p, miR-199a-5p, miR-214-3p, let-7a and miR-517a-3p as significantly up-regulated and miR-374b-5p, miR-378a-3p, miR-20b-5p and miR-30e-3p as significantly down-regulated. In patient tumour samples, we observed the highest median values of relative expression of miR-218-5p, miR-31-5p, miR-375-5p and miR-517a-3p, but also miR-20b-5p and miR-378a-3p, in metastatic tumour samples when compared with primary tumour or control samples. In TGCT patient plasma samples, we detected increased expression of miR-218-5p, miR-31-5p, miR-517a-3p and miR-375-5p when compared to healthy individuals. We propose that miR-218-5p, miR-31-5p, miR-375-5p, miR-517-3p, miR-20b-5p and miR-378a-3p represent a new panel of biomarkers for better prediction of chemoresistance and more aggressive phenotypes potentially underlying metastatic spread in non-seminomatous TGCTs. In addition, we provide predictions of the targets and functional and regulatory networks of selected miRNAs.<\/jats:p>","DOI":"10.3390\/ijms24032495","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:58:25Z","timestamp":1675054705000},"page":"2495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Integrated Microarray-Based Data Analysis of miRNA Expression Profiles: Identification of Novel Biomarkers of Cisplatin-Resistance in Testicular Germ Cell Tumours"],"prefix":"10.3390","volume":"24","author":[{"given":"Jan","family":"Ro\u0161ka","sequence":"first","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences-University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Danica","family":"Ivovi\u010d","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}]},{"given":"Lenka","family":"Wachsmannov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4637-0157","authenticated-orcid":false,"given":"Thomas","family":"Mueller","sequence":"additional","affiliation":[{"name":"University Clinic for Internal Medicine IV, Hematology\/Oncology, Medical Faculty of Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences-University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences-University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-5084","authenticated-orcid":false,"given":"Miroslav","family":"Chovanec","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-6932","authenticated-orcid":false,"given":"Dana","family":"Jurkovi\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3109\/02841861003782017","article-title":"NORDCAN\u2014a Nordic Tool for Cancer Information, Planning, Quality Control and Research","volume":"49","author":"Engholm","year":"2010","journal-title":"Acta Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ejca.2013.11.035","article-title":"Testicular Cancer Incidence to Rise by 25% by 2025 in Europe? 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