Roška Jan, Wachsmannová Lenka, Hurbanová Lenka, Šestáková Zuzana, Mueller Thomas, Jurkovičová Dana, Chovanec Miroslav
Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic.
University Clinic for Internal Medicine IV, Hematology/Oncology, Medical Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Oncotarget. 2020 Dec 22;11(51):4735-4753. doi: 10.18632/oncotarget.27844.
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, , , , , , , , , , , , , , and , 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.
睾丸生殖细胞肿瘤（TGCTs）因其对顺铂（CDDP）的特殊反应而成为一种可治愈性良好的恶性肿瘤。尽管治疗效果显著，但仍有大约5%的TGCT患者会产生顺铂耐药并死亡。TGCTs极高的治愈率使其成为研究顺铂敏感性分子机制的极具价值的模型系统。我们的研究旨在揭示顺铂耐药和敏感的TGCT细胞系之间的基因表达差异，从而确定可作为顺铂反应潜在生物标志物的候选基因。通过基因表达阵列，我们鉴定出281个在顺铂耐药的TGCT细胞系与敏感细胞系中差异表达的基因。通过RT-qPCR验证了25个变化倍数最高的基因的表达。其中，当所有顺铂耐药的TGCT细胞系与所有敏感细胞系两两组合时， 、 、 、 、 、 、 、 、 、 、 、 、 以及 在基因表达阵列和RT-qPCR中显示出相当的表达变化。所鉴定基因的产物是多能性因子，或参与细胞代谢、增殖或迁移等过程。我们认为，经过临床验证后，这些基因可作为预测生物标志物，用于早期检测TGCT患者的顺铂反应。
