Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Cierna Z 

PROVIDER: S-EPMC6945513 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Background</h4>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  ...[more]

Similar Datasets

| S-EPMC6769617 | biostudies-literature
| S-EPMC3708571 | biostudies-other
2019-08-29 | GSE136560 | GEO
| S-EPMC10241889 | biostudies-literature
| S-EPMC8510620 | biostudies-literature
| S-EPMC9916636 | biostudies-literature
| PRJNA562689 | ENA
| S-EPMC6683367 | biostudies-literature
| S-EPMC6199368 | biostudies-literature
| S-EPMC3388491 | biostudies-literature