Abstract
Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and access to care remain a challenge and whose survival lacks behind that of children diagnosed with histologically similar tumors. Understanding the tumor biology that differentiates children from AYA-RMS could provide critical information and drive new initiatives to improve the final outcome. MicroRNA (miRNA) and gene expression profiling (GEP) was evaluated in a RMS cohort of 49 tumor and 15 non-neoplastic tissues. miRNAs analysis identified miR-223 over-expression and miR-431 down-regulation in AYA, validated by Real-Time PCR and miRNA in situ hybridization (ISH). GEP analysis detected 793 age-correlated genes in tumors, of which 194 were anti-correlated. NOTCH2, FGFR1/2 were significantly down-modulated in AYA-RMS. miR-223 was associated with up-regulation of epithelial mesenchymal translation (EMT) and inflammatory pathways, whereas miR-431 was correlated to myogenic differentiation and muscle metabolism. GEP showed an increase in genes associated with CD4 memory resting cells and a decrease in genes associated with γδ T-cells in AYA-RMS. Immunohistochemistry (IHC) analysis demonstrated an increase of infiltrated CD4, CD8, and neutrophils in AYA-RMS tumors. Our results show that aggressiveness of AYA-RMS could be explained by differences in microenvironmental signal modulation mediated by tumor cells, suggesting a fundamental role of immune contexture in AYA-RMS development.
| Original language | English |
|---|---|
| Article number | 1380 |
| Journal | Cancers |
| Volume | 11 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2019 |
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Keywords
- Adolescents
- Gene expression
- Immune contexture
- MiRNA
- Pediatric tumors
- Rhabdomyosarcoma
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Age-related alterations in immune contexture are associated with aggressiveness in Rhabdomyosarcoma. / Gasparini, Patrizia; Fortunato, Orazio; De Cecco, Loris; Casanova, Michela; Iannó, Maria Federica; Carenzo, Andrea; Centonze, Giovanni; Milione, Massimo; Collini, Paola; Boeri, Mattia; Dugo, Matteo; Gargiuli, Chiara; Mensah, Mavis; Segale, Miriam; Bergamaschi, Luca; Chiaravalli, Stefano; Sensi, Maria Luisa; Massimino, Maura; Sozzi, Gabriella; Ferrari, Andrea.
In: Cancers, Vol. 11, No. 9, 1380, 09.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Age-related alterations in immune contexture are associated with aggressiveness in Rhabdomyosarcoma
AU - Gasparini, Patrizia
AU - Fortunato, Orazio
AU - De Cecco, Loris
AU - Casanova, Michela
AU - Iannó, Maria Federica
AU - Carenzo, Andrea
AU - Centonze, Giovanni
AU - Milione, Massimo
AU - Collini, Paola
AU - Boeri, Mattia
AU - Dugo, Matteo
AU - Gargiuli, Chiara
AU - Mensah, Mavis
AU - Segale, Miriam
AU - Bergamaschi, Luca
AU - Chiaravalli, Stefano
AU - Sensi, Maria Luisa
AU - Massimino, Maura
AU - Sozzi, Gabriella
AU - Ferrari, Andrea
PY - 2019/9
Y1 - 2019/9
N2 - Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and access to care remain a challenge and whose survival lacks behind that of children diagnosed with histologically similar tumors. Understanding the tumor biology that differentiates children from AYA-RMS could provide critical information and drive new initiatives to improve the final outcome. MicroRNA (miRNA) and gene expression profiling (GEP) was evaluated in a RMS cohort of 49 tumor and 15 non-neoplastic tissues. miRNAs analysis identified miR-223 over-expression and miR-431 down-regulation in AYA, validated by Real-Time PCR and miRNA in situ hybridization (ISH). GEP analysis detected 793 age-correlated genes in tumors, of which 194 were anti-correlated. NOTCH2, FGFR1/2 were significantly down-modulated in AYA-RMS. miR-223 was associated with up-regulation of epithelial mesenchymal translation (EMT) and inflammatory pathways, whereas miR-431 was correlated to myogenic differentiation and muscle metabolism. GEP showed an increase in genes associated with CD4 memory resting cells and a decrease in genes associated with γδ T-cells in AYA-RMS. Immunohistochemistry (IHC) analysis demonstrated an increase of infiltrated CD4, CD8, and neutrophils in AYA-RMS tumors. Our results show that aggressiveness of AYA-RMS could be explained by differences in microenvironmental signal modulation mediated by tumor cells, suggesting a fundamental role of immune contexture in AYA-RMS development.
AB - Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and access to care remain a challenge and whose survival lacks behind that of children diagnosed with histologically similar tumors. Understanding the tumor biology that differentiates children from AYA-RMS could provide critical information and drive new initiatives to improve the final outcome. MicroRNA (miRNA) and gene expression profiling (GEP) was evaluated in a RMS cohort of 49 tumor and 15 non-neoplastic tissues. miRNAs analysis identified miR-223 over-expression and miR-431 down-regulation in AYA, validated by Real-Time PCR and miRNA in situ hybridization (ISH). GEP analysis detected 793 age-correlated genes in tumors, of which 194 were anti-correlated. NOTCH2, FGFR1/2 were significantly down-modulated in AYA-RMS. miR-223 was associated with up-regulation of epithelial mesenchymal translation (EMT) and inflammatory pathways, whereas miR-431 was correlated to myogenic differentiation and muscle metabolism. GEP showed an increase in genes associated with CD4 memory resting cells and a decrease in genes associated with γδ T-cells in AYA-RMS. Immunohistochemistry (IHC) analysis demonstrated an increase of infiltrated CD4, CD8, and neutrophils in AYA-RMS tumors. Our results show that aggressiveness of AYA-RMS could be explained by differences in microenvironmental signal modulation mediated by tumor cells, suggesting a fundamental role of immune contexture in AYA-RMS development.
KW - Adolescents
KW - Gene expression
KW - Immune contexture
KW - MiRNA
KW - Pediatric tumors
KW - Rhabdomyosarcoma
UR - http://www.scopus.com/inward/record.url?scp=85073269901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073269901&partnerID=8YFLogxK
U2 - 10.3390/cancers11091380
DO - 10.3390/cancers11091380
M3 - Article
AN - SCOPUS:85073269901
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 9
M1 - 1380
ER -