Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer

Rafael Rosell, Giorgio Scagliotti, Kathleen D. Danenberg, Reginald V N Lord, Gerold Bepler, Silvia Novello, Janine Cooc, Lucio Crinò, José Javier Sánchez, Miquel Taron, Corrado Boni, Filippo De Marinis, Maurizio Tonato, Maurizio Marangolo, Felice Gozzelino, Franceso Di Costanzo, Massimo Rinaldi, Dennis Salonga, Craig Stephens

Research output: Contribution to journalArticlepeer-review

Abstract

Non-small-cell lung cancer patients with locally advanced or metastatic disease at the time of diagnosis show marginal response to chemotherapy in terms of tumor shrinkage, time to progression and median survival. The identification and implementation of predictive genetic markers of response-specific cytotoxic drugs is a priority of current research and future trials. In this study, we have used quantitative PCR to analyse expression of β-tubulin III, stathmln, RRM1, COX-2 and GSTP1 in mRNA isolated from paraffin-embedded tumor biopsies of 75 nonsmali-celi lung cancer patients treated as part of a large randomized trial. In total, 22 patients were treated with gemcitabine/cisplatin, 25 with vinoreibine/cisplatin and 28 with paclitaxei/carboplatin. There were no differences in clinical characteristics and transcript levels in the pretreatment biopsies according to treatment arm. Patients with low β-tubulin III levels had better response in the paclitaxei/carboplatin arm (P = 0.05), and those with low RRM1 levels showed a tendency to better response in the gemcitabine/cisplatin arm. Time to progression was influenced by β-tubulin III (P = 0.03) and stathmin (P = 0.05) levels in the vinorelbine/cisplatin arm, and there was a tendency toward correlation between β-tubulin III levels and time to progression in the paclitaxel/carboplatin arm. RRM1 levels influenced time to progression (P = 0.05) and even more so, survival (P = 0.0028) in the gemcitabine/cisplatin arm. The predictive value of β-tubulin III, stathmin and RRM1 should be tested in prospective customized chemotherapy trials, the results of which will help tailor chemotherapy to improve patient survival.

Original languageEnglish
Pages (from-to)3548-3553
Number of pages6
JournalOncogene
Volume22
Issue number23
DOIs
Publication statusPublished - Jun 5 2003

Keywords

  • β-tubulin III
  • Gene expression
  • NSCLC
  • RRM1
  • Stathmin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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