Analysis of the ATR-Chk1 and ATM-Chk2 pathways in male breast cancer revealed the prognostic significance of ATR expression.
Sci Rep
; 7(1): 8078, 2017 08 14.
Article
en En
| MEDLINE
| ID: mdl-28808232
ABSTRACT
The ATR-Chk1 and ATM-Chk2 pathways are central in DNA damage repair (DDR) and their over-activation may confer aggressive molecular features, being an adaptive response to endogenous DNA damage and oncogene-induced replication stress. Herein we investigated the ATR-Chk1 and ATM-Chk2 signalings in male breast cancer (MBC). The expression of DDR kinases (pATR, pATM, pChk1, pChk2, and pWee1) and DNA damage markers (pRPA32 and γ-H2AX) was evaluated by immunohistochemistry in 289 MBC samples to assess their association. Survival analyses were carried out in 112 patients. Survival curves were estimated with the Kaplan-Meier method and compared by log-rank test. Cox proportional regression models were generated to identify variables impacting survival outcomes. The expression of pATR conferred poorer survival outcomes (log rank p = 0.013, p = 0.007 and p = 0.010 for overall, 15- and 10-year survival, respectively). Multivariate Cox models of 10-year survival and overall indicated that pATR expression, alone or combined with pChk2, was an independent predictor of adverse outcomes (10-year survival pATR HR 2.74, 95% CI 1.23-6.10; pATR/pChk2 HR 2.92, 95% CI 1.35-6.33; overall survival pATR HR 2.58, 95% CI 1.20-5.53; pATR/pChk2 HR 2.89, 95% CI 1.37-6.12). Overall, the ATR/ATM-initiated molecular cascade seems to be active in a fraction of MBC patients and may represent a negative prognostic factor.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Neoplasias de la Mama Masculina
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Proteínas de la Ataxia Telangiectasia Mutada
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Quinasa de Punto de Control 2
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Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)
Tipo de estudio:
Prognostic_studies
Límite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia