Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours.

Autor: Cierna Z; Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Miskovska V; 1st Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.; St. Elisabeth Cancer Institute, Bratislava, Slovakia., Roska J; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia., Jurkovicova D; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia., Pulzova LB; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia., Sestakova Z; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia., Hurbanova L; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia., Machalekova K; St. Elisabeth Cancer Institute, Bratislava, Slovakia., Chovanec M; 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.; National Cancer Institute, Bratislava, Slovakia., Rejlekova K; St. Elisabeth Cancer Institute, Bratislava, Slovakia.; 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Svetlovska D; St. Elisabeth Cancer Institute, Bratislava, Slovakia.; Translational Research Unit, Comenius University, Bratislava, Slovakia., Kalavska K; St. Elisabeth Cancer Institute, Bratislava, Slovakia.; Translational Research Unit, Comenius University, Bratislava, Slovakia.; Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia., Kajo K; St. Elisabeth Cancer Institute, Bratislava, Slovakia., Babal P; Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.; Faculty Hospital with Policlinics Skalica a.s., Skalica, Slovakia., Mardiak J; St. Elisabeth Cancer Institute, Bratislava, Slovakia.; 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Ward TA; Department of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK., Mego M; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia.; 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.; National Cancer Institute, Bratislava, Slovakia.; Translational Research Unit, Comenius University, Bratislava, Slovakia., Chovanec M; Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia. miroslav.chovanec@savba.sk.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2020 Jan 06; Vol. 20 (1), pp. 17. Date of Electronic Publication: 2020 Jan 06.
DOI: 10.1186/s12885-019-6496-1
Abstrakt: Background: Germ cell tumours (GCTs) represent a highly curable malignity as they respond well to cisplatin (CDDP)-based chemotherapy. Nevertheless, a small proportion of GCT patients relapse or do not respond to therapy. As this might be caused by an increased capacity to repair CDDP-induced DNA damage, identification of DNA repair biomarkers predicting inadequate or aberrant response to CDDP, and thus poor prognosis for GCT patients, poses a challenge. The objective of this study is to examine the expression levels of the key nucleotide excision repair (NER) factors, XPA, ERCC1 and XPF, in GCT patients and cell lines.
Methods: Two hundred seven GCT patients' specimens with sufficient follow-up clinical-pathological data and pairwise combinations of CDDP-resistant and -sensitive GCT cell lines were included. Immunohistochemistry was used to detect the ERCC1, XPF and XPA protein expression levels in GCT patients' specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines.
Results: GCT patients with low XPA expression had significantly better overall survival than patients with high expression (hazard ratio = 0.38, 95% confidence interval: 0.12-1.23, p = 0.0228). In addition, XPA expression was increased in the non-seminomatous histological subtype, IGCCCG poor prognosis group, increasing S stage, as well as the presence of lung, liver and non-pulmonary visceral metastases. Importantly, a correlation between inadequate or aberrant CDDP response and XPA expression found in GCT patients was also seen in GCT cell lines.
Conclusions: XPA expression is an additional independent prognostic biomarker for stratifying GCT patients, allowing for improvements in decision-making on treatment for those at high risk of refractoriness or relapse. In addition, it could represent a novel therapeutic target in GCTs.
Databáze: MEDLINE
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