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. 2007 Nov 7;2(11):e1129.
doi: 10.1371/journal.pone.0001129.

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

Rafael Rosell  1 , Marcin Skrzypski, Ewa Jassem, Miquel Taron, Roberta Bartolucci, Jose Javier Sanchez, Pedro Mendez, Imane Chaib, Laia Perez-Roca, Amelia Szymanowska, Witold Rzyman, Francesco Puma, Grazyna Kobierska-Gulida, Raffaele Farabi, Jacek Jassem
Affiliations

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

Rafael Rosell et al. PLoS One. .

Abstract

Background: 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).

Methodology and principal findings: 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).

Conclusions: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Event-free (A,B) and median (C,D) survival according to expression of TRX (A,C) and BRCA1 (B,D).
See this image and copyright information in PMC

References

    1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18:581–592. - PubMed
    1. Strauss GM. Adjuvant chemotherapy of lung cancer: methodologic issues and therapeutic advances. Hematol Oncol Clin North Am. 2005;19:263–281, vi. - PubMed
    1. Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7:719–727. - PubMed
    1. Parmigiani G, Garrett-Mayer ES, Anbazhagan R, Gabrielson E. A cross-study comparison of gene expression studies for the molecular classification of lung cancer. Clin Cancer Res. 2004;10:2922–2927. - PubMed
    1. Potti A, Mukherjee S, Petersen R, Dressman HK, Bild A, et al. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med. 2006;355:570–580. - PubMed

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