Oncotarget

Research Papers:

Differential gene expression in cisplatin-resistant and -sensitive testicular germ cell tumor cell lines

Jan Roška, Lenka Wachsmannová, Lenka Hurbanová, Zuzana Šestáková, Thomas Mueller, Dana Jurkovičová and Miroslav Chovanec _

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Oncotarget. 2020; 11:4735-4753. https://doi.org/10.18632/oncotarget.27844

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Abstract

Jan Roška1, Lenka Wachsmannová1, Lenka Hurbanová1, Zuzana Šestáková1, Thomas Mueller2, Dana Jurkovičová1,* and Miroslav Chovanec1,*

1 Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic

2 University Clinic for Internal Medicine IV, Hematology/Oncology, Medical Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

* Co-senior authors

Correspondence to:

Miroslav Chovanec,email: miroslav.chovanec@savba.sk

Keywords: gene expression array; cisplatin; testicular germ cell tumors; prognostic biomarkers; pluripotency factors

Received: November 02, 2020     Accepted: November 30, 2020     Published: December 22, 2020

Copyright: © 2020 Roška et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Testicular germ cell tumors (TGCTs) represent a well curable malignity due to their exceptional response to cisplatin (CDDP). Despite remarkable treatment results, approximately 5% of TGCT patients develop CDDP resistance and die. Exceptional curability makes TGCTs a highly valuable model system for studying the molecular mechanisms of CDDP sensitivity. Our study was aimed at revealing difference in gene expression between the CDDP-resistant and -sensitive TGCT cell lines, and hence at identifying candidate genes that could serve as potential biomarkers of CDDP response. Using gene expression array, we identified 281 genes that are differentially expressed in CDDP-resistant compared to -sensitive TGCT cell lines. The expression of 25 genes with the highest fold change was validated by RT-qPCR. Of them, DNMT3L, GAL, IGFBP2, IGFBP7, L1TD1, NANOG, NTF3, POU5F1, SOX2, WNT6, ZFP42, ID2, PCP4, SLC40A1 and TRIB3, displayed comparable expression change in gene expression array and RT-qPCR, when all CDDP-resistant TGCT cell lines were pairwise combined with all -sensitive ones. Products of the identified genes are pluripotency factors, or are involved in processes, such as cell metabolism, proliferation or migration. We propose that, after clinical validation, these genes could serve as prognostic biomarkers for early detection of CDDP response in TGCT patients.


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