Abstract
ABSTRACT Background Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced NSCLC pts treated with chemotherapy, but not on an individual basis. As a secondary aim of a prospective study, we assessed the predictive (for response) and prognostic (for survival) values of miRNA expression in NSCLC pts treated by C (60 mg/m2 D1) and V (25 mg/m2, D1 + 8) in 1st line chemotherapy. Methods During the diagnostic bronchoscopy, a tumour 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 miR 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 and response by WHO criteria. Results From 180 pts screened between 04/2009 and 11/2011, 38 pts were eligible including 27 males, 26 pts with Karnofsky PS of 80-100, 20 adenocarcinomas and 30 stage IV. Sixteen partial responses (43%) were observed. After stepwise selection, a two miRNA (miR-149 and miR-375) predictive signature for response to CV (AUC 0.90, sensitivity 88%, negative predictive value 89%) which was related to progression-free survival (medians 12 and 17 months (ms), respectively, p = 0.047). Using a linear combination of the miRNA CT values with Cox's regression coefficients as weights, a prognostic score for survival including 4 miRNA (miR-200c, miR-424, miR-29c and miR-124) was identified. The signature distinguished pts with good (n = 18) and poor (n = 20) prognosis with median survival of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8), respectively (p Conclusions miRNA signatures are predictive of response and are prognostic for survival in patients with NSCLC treated with cisplatin-vinorelbine in 1st line. The validation of these results in an independent cohort, taking in consideration conventional prognostic factors, is ongoing. Disclosure All authors have declared no conflicts of interest.
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