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. 2013 Oct;4(10):1572-81.
doi: 10.18632/oncotarget.1157.

The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Laura Bonanno  1 , Carlota Costa, Margarita Majem, Jose J Sanchez, Ana Gimenez-Capitan, Ignacio Rodriguez, Alain Vergnenegre, Bartomeu Massuti, Adolfo Favaretto, Massimo Rugge, Cinta Pallares, Miquel Taron, Rafael Rosell
Affiliations

The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Laura Bonanno et al. Oncotarget. 2013 Oct.

Abstract

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 less than 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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Figures

Figure 1
Figure 1. The biological model providing the rationale for our choice of DNA repair components to evaluate as potential predictive markers in advanced NSCLC patients treated with platinum-based chemotherapy
Figure 2
Figure 2. Kaplan-Meier curves of (A) progression-free survival and (B) overall survival for all 115 patients
Figure 3
Figure 3. The expression levels of (A) BRCA1, (B) UBC9 and (C) 53BP1 in squamous versus non-squamous histology, with (D) median expression levels and P-values
Figure 4
Figure 4. Kaplan-Meier curves showing (A) progression-free survival and (B) overall survival in patients with low BRCA1 expression according to 53BP1 expression levels
Figure 5
Figure 5. Kaplan-Meier curves showing (A) progression-free survival and (B) overall survival in patients with high BRCA1 expression according to 53BP1 expression levels
Figure 6
Figure 6. Simplified hypothetical model of the potential interplay between BRCA1 and 53BP1 in DNA damage response, based on our clinical results
See this image and copyright information in PMC

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