The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy
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Laura Bonanno1,2, Carlota Costa2, Margarita Majem3, Jose Javier Sanchez4, Ana Gimenez-Capitan2, Ignacio Rodriguez5, Alain Vergnenegre6, Bartomeu Massuti7, Adolfo Favaretto1, Massimo Rugge8, Cinta Pallares3, Miquel Taron2,9, Rafael Rosell2,9
1 Second Medical Oncology Unit, Istituto Oncologico Veneto I.R.C.C.S, Via Gattamelata 64, Padova, Italia;
2 Pangaea Biotech S.L, USP Dexeus University Institute, Barcelona, Spain;
3 Hospital de Sant Pau, Barcelona, Spain;
4 Universidad Autonoma de Madrid, Madrid, Spain;
5 Unidad Epidemiología y Estadística, Departamento de Obstetricia, Ginecología y Reproducción, USP Dexeus University Institute, Barcelona, Spain;
6 Cluzeau Hospital, Limoges, France;
7 Hospital General de Alicante, Alicante, Spain;
8 Department of Medicine, Surgical Pathology and Cytopathology Unit, Università degli Studi di Padova, Padova, Italy;
9 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
Rafael Rosell, email:
Laura Bonanno, email:
Keywords: BRCA1, 53BP1, DNA repair, predictive modeling, platinum.
Received: July 3, 2013 Accepted: July 30, 2013 Published: July 31, 2013
Platinum-based chemotherapy is the standard first-line treatment for non-oncogene- addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy.
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