MicroRNA expression profiling predicts clinical outcome of carboplatin/paclitaxel-based therapy in metastatic melanoma treated on the ECOG-ACRIN trial E2603

摘要: Carboplatin/paclitaxel (CP), with or without sorafenib, result in objective response rates of 18–20 % unselected chemotherapy-naive patients. Molecular predictors survival and to CP-based chemotherapy metastatic melanoma (MM) are critical improving the therapeutic index. Intergroup trial E2603 randomized MM patients CP sorafenib. Expression data were collected from pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor tissues 115 823 enrolled on E2603. The selected balanced across treatment arms, BRAF status, clinical outcome. We generated using Nanostring array (microRNA (miRNA) expression) DNA-mediated annealing, selection, extension ligation (DASL)/Illumina microarrays (HT12 v4) (mRNA protocols optimized for FFPE samples. Integrative computational analysis was performed a novel Tree-guided Recursive Cluster Selection (T-ReCS) [1] algorithm select most informative features/genes, followed by TargetScan miRNA target prediction (Human v6.2) mirConnX [2] network inference. T-ReCS identified PLXNB1 as negatively associated progression-free (PFS) miR-659-3p primary positively PFS. differentially expressed based PFS but not arm, NRAS status. Dichotomized median (less vs greater than 4 months), expression significantly different. High distinguished responsive disease (complete partial response) stable disease. predicted gene targets include NFIX, which is transcription factor known interact c-Jun AP-1 context developmental processes This integrative implicates candidate predictive biomarker treated platinum-based may serve improve patient selection.