Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer |
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Authors: | Mette Winther Steen Knudsen Jesper Dahlgaard Thomas Jensen Anker Hansen Peter Buhl Jensen Trine Tramm Jan Alsner Marianne Nordsmark |
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Institution: | 1. Dept. of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark;2. Medical Prognosis Institute, Hoersholm, Denmark;3. Centre for Health Promotion and Rehabilitation, Faculty of Health Sciences, VIA University College, Aarhus, Denmark;4. Dept. of Pathology, Aarhus University Hospital, Aarhus, Denmark;5. Dept. of Oncology, Aarhus University Hospital, Aarhus, Denmark;University of Connecticut Health Center, UNITED STATES |
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Abstract: | BackgroundmiRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS).Material and MethodsThe study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS.ResultsA univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17–0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16–0.87)) and DSS (HR: 0.32 (0.12–0.87)).ConclusionThe miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer. |
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