Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours

作者：Mendoza J; Martinez J; Hernandez C; Perez Montiel D; Castro C; Fabian Morales E; Santibanez M; Gonzalez Barrios R; Diaz Chavez J; Andonegui M A; Reynoso N; Onate L F; Jimenez M A; Nunez M; Dyer R; Herrera L A^*

来源：British Journal of Cancer, 2013, 109(1): 68-75.

DOI：10.1038/bjc.2013.303

• DNA repair
• DNA repair proteins
• testicular tumours

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. %26lt;br%26gt;Methods: The expression of ERCC1 and XPA and the presence of gamma H2AX 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%26apos;s t- or chi(2)-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model. %26lt;br%26gt;Results: High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and gamma H2AX 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 %26gt; 14.43, and in ERCC1-positive and non-CPS patients the HR was %26gt; 11.86 (P %26lt; 0.001). %26lt;br%26gt;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.

• 出版日期2013-7-9