BRCA1: a novel prognostic factor in resected non-small-cell lung cancer

• Published in: PloS one Vol. 2; no. 11; p. e1129
• Main Authors: Rosell, Rafael, Skrzypski, Marcin, Jassem, Ewa, Taron, Miquel, Bartolucci, Roberta, Sanchez, Jose Javier, Mendez, Pedro, Chaib, Imane, Perez-Roca, Laia, Szymanowska, Amelia, Rzyman, Witold, Puma, Francesco, Kobierska-Gulida, Grazyna, Farabi, Raffaele, Jassem, Jacek
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.11.2007; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis; Anemia; Angiogenesis; Benzimidazole; Benzimidazoles; BRCA1 protein; BRCA1 Protein - genetics; Breast cancer; BUBR1 protein; Cadherin; Cadherins; Cancer; Cancer genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Chemotherapy; Cisplatin; Cohort Studies; Confidence intervals; Correlation; Deoxyribonucleic acid; DNA; DNA binding proteins; DNA methylation; DNA repair; Drugs; ERCC1 protein; Female; Gastric cancer; Gene expression; Genes; Hazards; Homology; Hospitals; Humans; Hypoxia; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lungs; Lymphocytes; Male; Medical research; Messenger RNA; Metastasis; Middle Aged; Molecular Biology/DNA Repair; N-Cadherin; NF-AT protein; Non-small cell lung cancer; Non-small cell lung carcinoma; Oncology; Oncology/Lung Cancer; Paraffin; Patients; Phosphodiesterase; Polymerase chain reaction; Prognosis; Protein expression; Proteins; Reductase; Reverse Transcriptase Polymerase Chain Reaction; Review boards; RNA, Messenger - genetics; Statistical models; Stomach cancer; Surgery; Survival; Survival Analysis; T cells; Thioredoxin; Thioredoxins; Transcription factors; Vascular endothelial growth factor; Yeast; Zinc; Zinc finger proteins; Poland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001129

Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1). We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04). Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated.