Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 134, Issue 8, Pages 2202-2211Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2014.85
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Funding
- clinical research education program
- CePORTED under CONDUITS
- Icahn School of Medicine NCATS [ULITR4067]
- NIH [T32HL094283]
- Lancaster General Hospital
- Bristol Myers Squibb
- Tisch Cancer Institute
- Dermatology Foundation
- Lancaster General Health
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Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using Nano String technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC) = 0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.
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