title: Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.
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.
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Hematology/Oncology Medical Specialists, Lancaster General Health, Lancaster, Pennsylvania, USA.
authors: Shanthi
authors: S
authors: Sivendran
authors: Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: rui.r.chang@mssm.edu.
authors: Rui
authors: R
authors: Chang
authors: Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Lisa
authors: L
authors: Pham
authors: Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Robert G
authors: RG
authors: Phelps
authors: Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Sara T
authors: ST
authors: Harcharik
authors: Department of Dermatology, Geisinger Health Systems, Dermatology Woodbine Danville, Danville, Pennsylvania, USA.
authors: Lawrence D
authors: LD
authors: Hall
authors: Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Sebastian G
authors: SG
authors: Bernardo
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Marina M
authors: MM
authors: Moskalenko
authors: Department of Dermatology, Geisinger Health Systems, Dermatology Woodbine Danville, Danville, Pennsylvania, USA.
authors: Meera
authors: M
authors: Sivendran
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Yichun
authors: Y
authors: Fu
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Ellen H
authors: EH
authors: de Moll
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Michael
authors: M
authors: Pan
authors: Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Jee Young
authors: JY
authors: Moon
authors: Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Sonali
authors: S
authors: Arora
authors: Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Ariella
authors: A
authors: Cohain
authors: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Analisa
authors: A
authors: DiFeo
authors: Department of Pathology, Geisinger Health Systems, Danville, Pennsylvania, USA.
authors: Tammie C
authors: TC
authors: Ferringer
authors: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, Englewood Hospital and Medical Center, Englewood, New Jersey, USA.
authors: Mikhail
authors: M
authors: Tismenetsky
authors: Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Cindy L
authors: CL
authors: Tsui
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Philip A
authors: PA
authors: Friedlander
authors: Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Michael K
authors: MK
authors: Parides
authors: Department of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Jacques
authors: J
authors: Banchereau
authors: Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
authors: Damien
authors: D
authors: Chaussabel
authors: Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Mark G
authors: MG
authors: Lebwohl
authors: Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Jedd D
authors: JD
authors: Wolchok
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, New York University, New York, New York, USA; Department of Dermatology, New York University, New York, New York, USA.
authors: Nina
authors: N
authors: Bhardwaj
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Steven J
authors: SJ
authors: Burakoff
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: William K
authors: WK
authors: Oh
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors: Karolina
authors: K
authors: Palucka
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Miriam
authors: M
authors: Merad
authors: Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Eric E
authors: EE
authors: Schadt
authors: Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: yvonne.saenger@mssm.edu.
authors: Yvonne M
authors: YM
authors: Saenger
mesh_terms: D001499:Bayes Theorem; D018801:CD2 Antigens / Q000032:analysis; D053263:Gene Regulatory Networks; D016158:Genes, p53; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging
chemical_list: D018801:CD2 Antigens