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

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Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours. / Cierna, Z.; Miskovska, V.; Roska, J.; Jurkovicova, D.; Pulzova, L.B.; Sestakova, Z.; Hurbanova, L.; Machalekova, K.; Chovanec, M.; Rejlekova, K.; Svetlovska, D.; Kalavska, K.; Kajo, K.; Babal, P.; Mardiak, J.; Ward, T.A.; Mego, M.; Chovanec, Miroslav.

In: BMC Cancer, Vol. 20, No. 1, 17, 06.01.2020.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Cierna, Z, Miskovska, V, Roska, J, Jurkovicova, D, Pulzova, LB, Sestakova, Z, Hurbanova, L, Machalekova, K, Chovanec, M, Rejlekova, K, Svetlovska, D, Kalavska, K, Kajo, K, Babal, P, Mardiak, J, Ward, TA, Mego, M & Chovanec, M 2020, 'Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours', BMC Cancer, vol. 20, no. 1, 17. https://doi.org/10.1186/s12885-019-6496-1

APA

Cierna, Z., Miskovska, V., Roska, J., Jurkovicova, D., Pulzova, L. B., Sestakova, Z., Hurbanova, L., Machalekova, K., Chovanec, M., Rejlekova, K., Svetlovska, D., Kalavska, K., Kajo, K., Babal, P., Mardiak, J., Ward, T. A., Mego, M., & Chovanec, M. (2020). Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours. BMC Cancer, 20(1), [17]. https://doi.org/10.1186/s12885-019-6496-1

Vancouver

Cierna Z, Miskovska V, Roska J, Jurkovicova D, Pulzova LB, Sestakova Z et al. Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours. BMC Cancer. 2020 Jan 6;20(1). 17. https://doi.org/10.1186/s12885-019-6496-1

Author

Cierna, Z. ; Miskovska, V. ; Roska, J. ; Jurkovicova, D. ; Pulzova, L.B. ; Sestakova, Z. ; Hurbanova, L. ; Machalekova, K. ; Chovanec, M. ; Rejlekova, K. ; Svetlovska, D. ; Kalavska, K. ; Kajo, K. ; Babal, P. ; Mardiak, J. ; Ward, T.A. ; Mego, M. ; Chovanec, Miroslav. / Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours. In: BMC Cancer. 2020 ; Vol. 20, No. 1.

Bibtex

@article{2b7179c7ef0742c9bbab10ff0e1dddeb,
title = "Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours",
abstract = "BackgroundGerm 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.MethodsTwo hundred seven GCT patients{\textquoteright} 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{\textquoteright} specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines.ResultsGCT 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.ConclusionsXPA 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.",
keywords = "Germ cell tumours, DNA repair, Nucleotide excision repair, XPA, Prognostic marker",
author = "Z. Cierna and V. Miskovska and J. Roska and D. Jurkovicova and L.B. Pulzova and Z. Sestakova and L. Hurbanova and K. Machalekova and M. Chovanec and K. Rejlekova and D. Svetlovska and K. Kalavska and K. Kajo and P. Babal and J. Mardiak and T.A. Ward and M. Mego and Miroslav Chovanec",
year = "2020",
month = jan,
day = "6",
doi = "10.1186/s12885-019-6496-1",
language = "English",
volume = "20",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours

AU - Cierna, Z.

AU - Miskovska, V.

AU - Roska, J.

AU - Jurkovicova, D.

AU - Pulzova, L.B.

AU - Sestakova, Z.

AU - Hurbanova, L.

AU - Machalekova, K.

AU - Chovanec, M.

AU - Rejlekova, K.

AU - Svetlovska, D.

AU - Kalavska, K.

AU - Kajo, K.

AU - Babal, P.

AU - Mardiak, J.

AU - Ward, T.A.

AU - Mego, M.

AU - Chovanec, Miroslav

PY - 2020/1/6

Y1 - 2020/1/6

N2 - BackgroundGerm 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.MethodsTwo 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.ResultsGCT 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.ConclusionsXPA 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.

AB - BackgroundGerm 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.MethodsTwo 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.ResultsGCT 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.ConclusionsXPA 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.

KW - Germ cell tumours

KW - DNA repair

KW - Nucleotide excision repair

KW - XPA

KW - Prognostic marker

U2 - 10.1186/s12885-019-6496-1

DO - 10.1186/s12885-019-6496-1

M3 - Journal article

VL - 20

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 17

ER -