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Genes 2016, 7(12), 124; doi:10.3390/genes7120124

microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response

1
Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
2
Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
3
Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
4
Melanoma and Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: George A. Calin and Muller Fabbri
Received: 9 October 2016 / Revised: 24 November 2016 / Accepted: 5 December 2016 / Published: 14 December 2016
(This article belongs to the Special Issue microRNAs and Other Non-Coding RNAs in Human Diseases)
View Full-Text   |   Download PDF [7591 KB, uploaded 14 December 2016]   |  

Abstract

Sentinel node biopsy (SNB) is a main staging biomarker in melanoma and is the first lymph node to drain the tumor, thus representing the immunological site where anti-tumor immune dysfunction is established and where potential prognostic immune markers can be identified. Here we analyzed microRNA (miR) profiles in archival tumor-positive SNBs derived from melanoma patients with different outcomes and performed an integrated analysis of transcriptional data to identify deregulated immune signaling networks. Twenty-six miRs were differentially expressed in melanoma-positive SNB samples between patients with disease progression and non-progressing patients, the majority being previously reported in the regulation of immune responses. A significant variation in miR expression levels was confirmed in an independent set of SNB samples. Integrated information from genome-wide transcriptional profiles and in vitro assessment in immune cells led to the identification of miRs associated with the regulation of the TNF receptor superfamily member 8 (TNFRSF8) gene encoding the CD30 receptor, a marker increased in lymphocytes of melanoma patients with progressive disease. These findings indicate that miRs are involved in the regulation of pathways leading to immune dysfunction in the sentinel node and may provide valuable markers for developing prognostic molecular signatures for the identification of stage III melanoma patients at risk of recurrence. View Full-Text
Keywords: microRNA; sentinel node biopsy; melanoma; immunosuppression; CD30 microRNA; sentinel node biopsy; melanoma; immunosuppression; CD30
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MDPI and ACS Style

Vallacchi, V.; Camisaschi, C.; Dugo, M.; Vergani, E.; Deho, P.; Gualeni, A.; Huber, V.; Gloghini, A.; Maurichi, A.; Santinami, M.; Sensi, M.; Castelli, C.; Rivoltini, L.; Rodolfo, M. microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response. Genes 2016, 7, 124.

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