Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer
Entity
UAM. Departamento de Medicina Preventiva y Salud Pública y MicrobiologíaPublisher
BioMed CentralDate
2016Citation
10.1186/s12885-016-2339-5
BMC Cancer 16 (2016): 312
ISSN
1471-2407DOI
10.1186/s12885-016-2339-5Funded by
Work in Dr. Rafael Rosell’s laboratory was partially supported by a grant from “La Caixa Foundation”Editor's Version
http://dx.doi.org/10.1186/s12885-016-2339-5Subjects
BRCA1; HERC2; Non-small-cell lung cancer; Platinum; Predictive markers; DNA repair; MedicinaRights
© 2016 Bonanno et al.Abstract
Background: BRCA1 is a main component of homologous recombination and induces resistance to platinum in
preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate
the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit
BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the
recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model.
Methods: We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non-small-cell lung
cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of
BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as
cut-off point.
Results: The median progression-free survival of all 71 patients was 7.2 months whereas the median overall survival
of the study population was 10.7 months. Among patients with low BRCA1 expression, the median PFS was 7.4 months
in the presence of low HERC2 levels and 5.9 months for patients expressing high HERC2 levels (p = 0.01). The median
OS was 15.3 months for patients expressing low levels of both genes and 7.4 months for those with low BRCA1 but
high HERC2 (p = 0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology
Group performance status 0–1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of
progression (p = 0.03) and of death (p = 0.004).
Conclusions: These findings confirm the potentiality of integrated DNA repair components analysis in predicting the
sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the
way for further refinement of the BRCA1 predictive model
Files in this item
Google Scholar:Bonanno, Laura
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Costa, Carlota
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Majem, Margarita
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Sánchez, José Javier
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Rodríguez, Ignacio
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Gimenez-Capitan, Ana
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Molina-Vila, Miquel Ángel
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Vergnenegre, Alain
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Massuti, Bartomeu
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Favaretto, Adolfo
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Rugge, Massimo
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Pallares, Cinta
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Taron, Miquel
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Rosell, Rafael
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