title: Identification of microRNA-based signatures for response and survival for non-small cell lung cancer treated with cisplatin-vinorelbine A ELCWP prospective study.
abstract: Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate individual prediction. MicroRNA (miRNA) are non-coding RNAs regulating gene expression. In a prospective study, we assessed the predictive value for response and survival of tumour miRNA in NSCLC patients treated by 1st line cisplatin and vinorelbine. miRNA expression was analysed on a biopsy obtained during the diagnostic bronchoscopy, using TaqMan Low Density Arrays. The signature for response was derived using logistic regression with stepwise variable selection. The associations between overall survival and miRNA expression levels were estimated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models to estimate the hazard ratios. In total, 38 patients with adequate tumour biopsies, treated with cisplatin-vinorelbine were included: male (n = 27), 80-100 Karnofsky PS (n = 27), adenocarcinoma (n = 20), stage IV (n = 30). One patient was considered not assessable for response but remained included in the survival analyses. Out of the 37 patients assessable for response, 16 partial responses (43%) were observed. A two miRNA signature (miR-149 and miR-375) was found predictive for response and was also associated to progression-free survival (p = 0.05). Using a linear combination of the miR CT values with Cox's regression coefficients as weights, we constructed a prognostic score for overall survival including four miRNA (miR-200c, miR-424, miR-29c and miR-124). The signature distinguished patients with good (n = 18) and poor (n = 20) prognosis with respective median survival times of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p < 0.001; hazard ratio 21.1, 95% CI 4.7-94.9).
  
  
  CONCLUSIONS
  miRNA signature allows predicting response and is of prognostic value for survival in patients with NSCLC treated with first line cisplatin and vinorelbine.
authors.affiliation: Department of Oncological Intensive Care and Emergencies & Thoracic Oncology, Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: thierry.berghmans@bordet.be.
authors.forename: T
authors.initials: T
authors.lastname: Berghmans
authors.forename: L
authors.initials: L
authors.lastname: Ameye
authors.forename: L
authors.initials: L
authors.lastname: Willems
authors.forename: M
authors.initials: M
authors.lastname: Paesmans
authors.forename: C
authors.initials: C
authors.lastname: Mascaux
authors.forename: J J
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: A P
authors.initials: AP
authors.lastname: Meert
authors.forename: A
authors.initials: A
authors.lastname: Scherpereel
authors.forename: A B
authors.initials: AB
authors.lastname: Cortot
authors.forename: I
authors.initials: I
authors.lastname: Cstoth
authors.forename: T
authors.initials: T
authors.lastname: Dernies
authors.forename: L
authors.initials: L
authors.lastname: Toussaint
authors.forename: N
authors.initials: N
authors.lastname: Leclercq
authors.forename: J P
authors.initials: JP
authors.lastname: Sculier
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011446:Prospective Studies; D059467:Transcriptome; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D035683:MicroRNAs; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Chemotherapy; Non small cell lung carcinoma; Prognosis; Response prediction; Survival; microRNA