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.
| Original language | English |
|---|---|
| Article number | 124 |
| Journal | Genes |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 14 2016 |
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Keywords
- CD30
- Immunosuppression
- Melanoma
- MicroRNA
- Sentinel node biopsy
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
MicroRNA expression in sentinel nodes fromprogressing melanoma patients identifies networks associated with dysfunctional immune response. / Vallacchi, Viviana; Camisaschi, Chiara; Dugo, Matteo; Vergani, Elisabetta; Deho, Paola; Gualeni, Ambra Vittoria; Huber, Veronica; Gloghini, Annunziata; Maurichi, Andrea; Santinami, Mario; Sensi, Marialuisa; Castelli, Chiara; Rivoltini, Licia; Rodolfo, Monica.
In: Genes, Vol. 7, No. 12, 124, 14.12.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA expression in sentinel nodes fromprogressing melanoma patients identifies networks associated with dysfunctional immune response
AU - Vallacchi, Viviana
AU - Camisaschi, Chiara
AU - Dugo, Matteo
AU - Vergani, Elisabetta
AU - Deho, Paola
AU - Gualeni, Ambra Vittoria
AU - Huber, Veronica
AU - Gloghini, Annunziata
AU - Maurichi, Andrea
AU - Santinami, Mario
AU - Sensi, Marialuisa
AU - Castelli, Chiara
AU - Rivoltini, Licia
AU - Rodolfo, Monica
PY - 2016/12/14
Y1 - 2016/12/14
N2 - 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.
AB - 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.
KW - CD30
KW - Immunosuppression
KW - Melanoma
KW - MicroRNA
KW - Sentinel node biopsy
UR - http://www.scopus.com/inward/record.url?scp=85006827183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006827183&partnerID=8YFLogxK
U2 - 10.3390/genes7120124
DO - 10.3390/genes7120124
M3 - Article
AN - SCOPUS:85006827183
VL - 7
JO - Genes
JF - Genes
SN - 2073-4425
IS - 12
M1 - 124
ER -