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; 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

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

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

Authors

Laura Bonanno¹, 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

Affiliation

¹ Second Medical Oncology Unit, Istituto Oncologico Veneto I.R.C.C.S, Via Gattamelata 64, Padova, Italia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
BRCA1 Protein / biosynthesis
BRCA1 Protein / genetics*
Biomarkers, Tumor / biosynthesis
Biomarkers, Tumor / genetics
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Disease-Free Survival
Female
Gene Expression
Humans
Intracellular Signaling Peptides and Proteins / biosynthesis
Intracellular Signaling Peptides and Proteins / genetics*
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Male
Middle Aged
Organoplatinum Compounds / administration & dosage
Prognosis
RNA, Messenger / analysis
RNA, Messenger / biosynthesis*
RNA, Messenger / genetics
Sex Factors
Signal Transduction
Tumor Suppressor p53-Binding Protein 1

Substances

BRCA1 Protein
Biomarkers, Tumor
Intracellular Signaling Peptides and Proteins
Organoplatinum Compounds
RNA, Messenger
TP53BP1 protein, human
Tumor Suppressor p53-Binding Protein 1