title: Prospective Validation Obtained in a Similar Group of Patients and with Similar High Throughput Biological Tests Failed to Confirm Signatures for Prediction of Response to Chemotherapy and Survival in Advanced NSCLC: A Prospective Study from the European Lung Cancer Working Party.
abstract: OBJECTIVE
  Cisplatin doublets are standard 1st line treatment for advanced non-small cell lung cancer (NSCLC), without accurate predictor for response and survival, but important toxicity. Our aims were to identify predictive (for response) and prognostic (for survival) biological signatures in patients with NSCLC using messenger RNAs (mRNA) and miRNA expression.
  
  
  METHODS
  Patients with pathologically proven untreated NSCLC, receiving 1st line cisplatin-vinorelbine and with an assessable lesion were eligible. A bronchial biopsy was lysed into Tripure Isolation Reagent on ice, snap frozen, and stored at -80°C. mRNA expression was analyzed using microarrays Agilent Technologies. miRNA expression was assessed using TaqMan Low Density Arrays (756 human miR panel, Applied Biosystems). Validation was performed by RT-PCR on the selected genes. Survival was measured from the registration date and response assessed by WHO criteria.
  
  
  RESULTS
  Biopsies for transcriptomic analyses were obtained from 60 consecutive patients. No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets. In the derivation set (n = 38 patients), two mRNA and one miRNA predictive signatures for response were obtained. One mRNA and one miRNA prognostic signatures were derived from the first set, allowing an adequate distinction of patients with good and poor overall and progression-free survivals. None of these signatures could be validated in the validation set (n = 22 patients).
  
  
  CONCLUSIONS
  In this prospective study with advanced NSCLC treated with cisplatin-vinorelbine, we were able to derive with high throughput techniques predictive and prognostic signatures based on transcriptomic analyses. However, these results could not be reproduced in an independent validation set. The role of miRNA and mRNA as predictive or prognostic factors remains a research topic and the use of high throughput technology in that context questionable. The ClinicalTrials.gov study identifier is NCT00864266 (www.clinicaltrials.gov).
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors: Thierry
authors: T
authors: Berghmans
authors: Data Centre, Institut Jules Bordet, Université Libre de Bruxelles (ULB) , Brussels , Belgium.
authors: Lieveke
authors: L
authors: Ameye
authors: Department of Pulmonary and Thoracic Oncology, Centre Hospitalier Régional Universitaire de Lille , Lille , France.
authors: Jean-Jacques
authors: JJ
authors: Lafitte
authors: Department of Pneumology, Grand Hôpital de Charleroi, site Saint-Joseph , Gilly , Belgium.
authors: Benoît
authors: B
authors: Colinet
authors: Department of Pulmonary and Thoracic Oncology, Centre Hospitalier Régional Universitaire de Lille , Lille , France.
authors: Alexis
authors: A
authors: Cortot
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors: Ingrid
authors: I
authors: CsToth
authors: Department of Oncology, Hôpital Ambroise Paré , Mons , Belgium.
authors: Stéphane
authors: S
authors: Holbrechts
authors: Department of Pneumology, CH Charleroi , Charleroi , Belgium.
authors: Jacques
authors: J
authors: Lecomte
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium ; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre , Toronto, ON , Canada.
authors: Céline
authors: C
authors: Mascaux
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors: Anne-Pascale
authors: AP
authors: Meert
authors: Data Centre, Institut Jules Bordet, Université Libre de Bruxelles (ULB) , Brussels , Belgium.
authors: Marianne
authors: M
authors: Paesmans
authors: Department of Pneumology, CHR St Joseph , Warquignies , Belgium.
authors: Michel
authors: M
authors: Richez
authors: Department of Pulmonary and Thoracic Oncology, Centre Hospitalier Régional Universitaire de Lille , Lille , France.
authors: Arnaud
authors: A
authors: Scherpereel
authors: Department of Pneumology, CH Mouscron , Mouscron , Belgium.
authors: Christian
authors: C
authors: Tulippe
authors: Laboratory of Molecular and Cellular Biology, Université de Liège , Gembloux , Belgium.
authors: Luc
authors: L
authors: Willems
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors: Tiffany
authors: T
authors: Dernies
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors: Nathalie
authors: N
authors: Leclercq
authors: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors: Jean-Paul
authors: JP
authors: Sculier
keywords: chemotherapy; mRNA; miRNA; non-small cell lung cancer; survival