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Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.
Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G; Harcharik, Sara T; Hall, Lawrence D; Bernardo, Sebastian G; Moskalenko, Marina M; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C; Tismenetsky, Mikhail; Tsui, Cindy L; Friedlander, Philip A; Parides, Michael K; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G; Wolchok, Jedd D; Bhardwaj, Nina; Burakoff, Steven J; Oh, William K; Palucka, Karolina; Merad, Miriam; Schadt, Eric E; Saenger, Yvonne M.
Afiliação
  • Sivendran S; 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.
  • Chang R; 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.
  • Pham L; Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Phelps RG; 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.
  • Harcharik ST; Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Hall LD; Department of Dermatology, Geisinger Health Systems, Dermatology Woodbine Danville, Danville, Pennsylvania, USA.
  • Bernardo SG; Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Moskalenko MM; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Sivendran M; Department of Dermatology, Geisinger Health Systems, Dermatology Woodbine Danville, Danville, Pennsylvania, USA.
  • Fu Y; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • de Moll EH; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Pan M; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Moon JY; Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Arora S; Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Cohain A; Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • DiFeo A; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.
  • Ferringer TC; Department of Pathology, Geisinger Health Systems, Danville, Pennsylvania, USA.
  • Tismenetsky M; 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.
  • Tsui CL; Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Friedlander PA; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Parides MK; Center for Biostatistics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Banchereau J; Department of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Chaussabel D; Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
  • Lebwohl MG; Department of Dermatology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Wolchok JD; Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  • Bhardwaj N; 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.
  • Burakoff SJ; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Oh WK; Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Palucka K; 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.
  • Merad M; 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.
  • Schadt EE; Department of Genetics and Genomic Science, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Saenger YM; 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.
J Invest Dermatol ; 134(8): 2202-2211, 2014 Aug.
Article em En | MEDLINE | ID: mdl-24522433
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Screening_studies Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Screening_studies Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article