Abstract
e18006 Background: Main prognostic factors for survival in NSCLC pts are stage and performance status (PS) while sex, histology and others are reported. However, these variables do not allow predicting individual prognosis, justifying further research. MiRNA are small non-coding RNAs regulating gene expression. As a secondary aim of a prospective study, we looked at the prognostic value of tumour miRNA on survival in NSCLC pts treated by cisplatin (60 mg/m2 D1) and vinorelbine (25 mg/m2, D1+8) 1st line chemotherapy. Methods: During the diagnostic bronchoscopy, a biopsy was lysed into Tripure Isolation Reagent (Roche Diagnostics) on ice, snap frozen and stored at -80°C. MiRNA expression was assessed using TaqMan Low Density Arrays (756 human miRNA panel, Applied Biosystems) and normalized using the delta delta CT method to RNU48 (SNORD48) CT value for every sample. Survival was measured from the registration date. Results: The main characteristics of 38 eligible pts were: median age 60 years, male 27 (71%), 80-100 Karnofsky PS in 26 (68%), adenocarcinoma 20 (53%), stage IV 30 (79%). At time of analysis, 25 pts were dead. After stepwise selection among 756 analysed miRNA, a combination of 4 miRNA including miR-200c, miR-424, miR-29c and miR-124 provided a prognostic signature for survival. Using a linear combination of the miRNA CT values with Cox's regression coefficients as weights, we constructed a prognostic score. With a cut-off of 52, the signature distinguished pts with good (n = 18) and poor (n = 20) prognosis with respective median survival 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). The same signature discriminated pts with “good progression-free survival” (median 19.8 months; 95% CI 15.3-33.8) from the others (median 9.1 months; 95% CI 6.3-15.5) (p <0.001; hazard ratio 3.8, 95% CI 1.7-8.7). Conclusions: A 4 miRNA signature is associated with improved survival in patients with advanced stage NSCLC treated with 1st line cisplatin and vinorelbine. These results need confirmation in an independent cohort and the signature has to be compared to conventional prognostic factors.
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