PLoS ONE (Jan 2008)

Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.

  • Ioannis Boukovinas,
  • Chara Papadaki,
  • Pedro Mendez,
  • Miquel Taron,
  • Dimitris Mavroudis,
  • Anastasios Koutsopoulos,
  • Maria Sanchez-Ronco,
  • Jose Javier Sanchez,
  • Maria Trypaki,
  • Eustathios Staphopoulos,
  • Vassilis Georgoulias,
  • Rafael Rosell,
  • John Souglakos

DOI
https://doi.org/10.1371/journal.pone.0003695
Journal volume & issue
Vol. 3, no. 11
p. e3695

Abstract

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BackgroundOverexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC) patients.Methodology and principal findingsTumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01) and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36). As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; pConclusionsThe mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.