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J Invest Dermatol. 2014 Aug;134(8):2202-11. doi: 10.1038/jid.2014.85. Epub 2014 Feb 12.

Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

Author information

1
1] Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Hematology/Oncology Medical Specialists, Lancaster General Health, Lancaster, Pennsylvania, USA.
2
Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3
1] Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
4
Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
5
Department of Dermatology, Geisinger Health Systems, Dermatology Woodbine Danville, Danville, Pennsylvania, USA.
6
Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
7
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.
8
Department of Pathology, Geisinger Health Systems, Danville, Pennsylvania, USA.
9
1] Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Pathology, Englewood Hospital and Medical Center, Englewood, New Jersey, USA.
10
Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
11
Department of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
12
Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
13
Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
14
1] Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Pathology, New York University, New York, New York, USA [3] Department of Dermatology, New York University, New York, New York, USA.
15
1] Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Baylor Institute for Immunology Research, Dallas, Texas, USA.
16
1] Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
17
1] Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Abstract

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 NanoString 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.

PMID:
24522433
PMCID:
PMC4291112
DOI:
10.1038/jid.2014.85
[Indexed for MEDLINE]
Free PMC Article
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