Integrated Microarray-Based Data Analysis of miRNA Expression Profiles: Identification of Novel Biomarkers of Cisplatin-Resistance in Testicular Germ Cell Tumours.
biomarker
cisplatin
miRNA
miRNA microarray
testicular germ cell tumour
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
27 Jan 2023
27 Jan 2023
Historique:
received:
13
12
2022
revised:
13
01
2023
accepted:
25
01
2023
entrez:
11
2
2023
pubmed:
12
2
2023
medline:
15
2
2023
Statut:
epublish
Résumé
Testicular germ cell tumours (TGCTs) are the most common solid malignancy among young men, and their incidence is still increasing. 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.
Identifiants
pubmed: 36768818
pii: ijms24032495
doi: 10.3390/ijms24032495
pmc: PMC9916636
pii:
doi:
Substances chimiques
Cisplatin
Q20Q21Q62J
MicroRNAs
0
Biomarkers
0
Biomarkers, Tumor
0
MIRN214 microRNA, human
0
MIRN218 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : VEGA Grant Agency of the Slovak Republic
ID : 2/0056/21
Organisme : Slovak Research and Development Agency
ID : APVV-19-0286
Organisme : Ministry of Education, Science Research and Sport of the Slovak Republic
ID : MVTS 34097104
Organisme : European Regional Development Fund, Integrated Infrastructure Operational Program
ID : ITMS: 313011AFG5
Organisme : Research Center of Portuguese Institute of Porto
ID : CI-IPOP-27-2016
Organisme : Research Center of Portuguese Institute of Porto
ID : CI-IPOP-74-2016
Organisme : Ministry of Health of the Slovak Republic
ID : 2019/57-BMCSAV-1
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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