title: The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy.
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.
authors.affiliation: Second Medical Oncology Unit, Istituto Oncologico Veneto I.R.C.C.S, Via Gattamelata 64, Padova, Italia.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonanno
authors.forename: Carlota
authors.initials: C
authors.lastname: Costa
authors.forename: Margarita
authors.initials: M
authors.lastname: Majem
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Ana
authors.initials: A
authors.lastname: Gimenez-Capitan
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rodriguez
authors.forename: Alain
authors.initials: A
authors.lastname: Vergnenegre
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Adolfo
authors.initials: A
authors.lastname: Favaretto
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Cinta
authors.initials: C
authors.lastname: Pallares
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012737:Sex Factors; D015398:Signal Transduction; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1