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Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell
J Mendoza1, J Martínez, C Hernández
1Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan)-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Avenida San Fernando 22, México D.F. 14080, México.
Background:
Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs.
Methods:
The expression of ERCC1 and XPA and the presence of γH2AX were evaluated in cancer cell lines and in fresh ns-TGCTs. The ERCC1 protein was also determined in ns-TGCTs. The differences between CPS and non-CPS cell lines and patients were analysed by Student's t- or χ(2)-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model.
Results:
High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and γH2AX expressions were augmented after cisplatin treatment. Increased ERCC1 expression was also identified in non-CPS patients. Neither polymorphism was associated with either CPS or OS. The presence of ERCC1 was associated with non-CPS (P=0.05) and adjusted in the prognosis groups. The HR in ERCC1-negative and non-CPS patients was >14.43, and in ERCC1-positive and non-CPS patients the HR was >11.86 (P<0.001).
Conclusions:
High levels of ERCC1 were associated with non-CPS, suggesting that ERCC1 could be used as a potential indicator of the response to cisplatin and prognosis in ns-TGCTs.
Insights
High ERCC1 expression indicates poor cisplatin sensitivity in non-seminomatous testicular germ cell tumors. This finding suggests ERCC1 could predict treatment response and prognosis in these patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cisplatin is a key chemotherapy for testicular germ cell tumors (TGCTs), with over 80% cure rates.
- Nucleotide-excision repair (NER) pathway proteins influence cisplatin sensitivity.
- This study investigates NER proteins and their polymorphisms in relation to cisplatin sensitivity and overall survival in non-seminomatous TGCTs (ns-TGCTs).
Purpose of the Study:
- To explore the association between NER proteins, specifically ERCC1 and XPA, and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) in ns-TGCT patients.
- To evaluate the role of ERCC1 expression as a potential biomarker for cisplatin response and prognosis in ns-TGCTs.
Main Methods:
- ERCC1, XPA, and γH2AX expression were assessed in ns-TGCT cell lines and patient samples.
- ERCC1 protein levels were quantified in ns-TGCT tissues.
- Statistical analyses included Student's t-tests, chi-squared tests, log-rank tests, and Cox proportional hazards models to compare cisplatin-sensitive (CPS) and non-sensitive (non-CPS) groups and analyze overall survival (OS).
Main Results:
- High ERCC1 expression was observed in non-CPS cells and patients.
- ERCC1 and γH2AX expression increased after cisplatin treatment.
- No association was found between ERCC1/XPA polymorphisms and CPS or OS.
- ERCC1 presence correlated with non-CPS (P=0.05).
- High hazard ratios (HRs) for poor prognosis were observed in both ERCC1-negative (>14.43) and ERCC1-positive (>11.86) non-CPS patients (P<0.001).
Conclusions:
- Elevated ERCC1 levels are significantly associated with non-CPS in ns-TGCTs.
- ERCC1 may serve as a predictive biomarker for cisplatin response in ns-TGCT patients.
- ERCC1 expression could be a valuable prognostic indicator for overall survival in ns-TGCTs.
