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

Shanthi Sivendran, Rui Chang, Lisa Pham, Robert G. Phelps, Sara T. Harcharik, Lawrence D. Hall, Sebastian G. Bernardo, Marina M. Moskalenko, Meera Sivendran, Yichun Fu, Ellen H. De Moll, Michael Pan, Jee Young Moon, Sonali Arora, Ariella Cohain, Analisa Difeo, Tammie C. Ferringer, Mikhail Tismenetsky, Cindy L. Tsui, Philip A. FriedlanderMichael K. Parides, Jacques Banchereau, Damien Chaussabel, Mark G. Lebwohl, Jedd D. Wolchok, Nina Bhardwaj, Steven J. Burakoff, William K. Oh, Karolina Palucka, Miriam Merad, Eric E. Schadt, Yvonne M. Saenger

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2202-2211
Number of pages10
JournalJournal of Investigative Dermatology
Volume134
Issue number8
DOIs
Publication statusPublished - Aug 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Sivendran, S., Chang, R., Pham, L., Phelps, R. G., Harcharik, S. T., Hall, L. D., Bernardo, S. G., Moskalenko, M. M., Sivendran, M., Fu, Y., De Moll, E. H., Pan, M., Moon, J. Y., Arora, S., Cohain, A., Difeo, A., Ferringer, T. C., Tismenetsky, M., Tsui, C. L., ... Saenger, Y. M. (2014). Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease. Journal of Investigative Dermatology, 134(8), 2202-2211. https://doi.org/10.1038/jid.2014.85