TY - JOUR
T1 - CXCL14, CXCR7 expression and CXCR4 splice variant ratio associate with survival and metastases in Ewing sarcoma patients
AU - Sand, L. G L
AU - Scotlandi, K.
AU - Berghuis, D.
AU - Snaar-Jagalska, B. E.
AU - Picci, P.
AU - Schmidt, T.
AU - Szuhai, K.
AU - Hogendoorn, P. C W
PY - 2015
Y1 - 2015
N2 - Purpose Ewing sarcoma (EWS) is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. Our goal was to identify novel predictive biomarkers for these patients, focusing on chemokines, specifically genes involved in the CXCR4-pathway because of their established role in metastasis and tumour growth. Methods Total RNA isolated from therapy-naïve tumour samples (n = 18; panel I) and cell lines (n = 21) was used to study expression of CXCR4-pathway related genes and CXCR4 splice variants (CXCR4-2: Small and CXCR4-1: Large) by RT-Q-PCR. Expression levels were correlated to overall survival (OS) and event free survival (EFS). Study results were validated in an independent series of 26 tumour samples (panel II) from therapy-naïve tumour samples. Results CXCL12, CXCR4, CXCR7 and CXCL14 were expressed and high CXCR7 and CXCL14 expression showed a positive correlation with EFS and OS and a negative correlation with metastasis development. Both splice variants CXCR4 were expressed in cell lines and tumour samples and CXCR4-1/CXCR4-2 ratio was significantly higher in tumour samples compared to cell lines and correlated with an improved EFS and OS. The results from the test panel were validated in an independent sample panel. Conclusions We identified a set of genes involved in CXCR4 signalling that may be used as a marker to predict survival and metastasis development in Ewing sarcoma.
AB - Purpose Ewing sarcoma (EWS) is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. Our goal was to identify novel predictive biomarkers for these patients, focusing on chemokines, specifically genes involved in the CXCR4-pathway because of their established role in metastasis and tumour growth. Methods Total RNA isolated from therapy-naïve tumour samples (n = 18; panel I) and cell lines (n = 21) was used to study expression of CXCR4-pathway related genes and CXCR4 splice variants (CXCR4-2: Small and CXCR4-1: Large) by RT-Q-PCR. Expression levels were correlated to overall survival (OS) and event free survival (EFS). Study results were validated in an independent series of 26 tumour samples (panel II) from therapy-naïve tumour samples. Results CXCL12, CXCR4, CXCR7 and CXCL14 were expressed and high CXCR7 and CXCL14 expression showed a positive correlation with EFS and OS and a negative correlation with metastasis development. Both splice variants CXCR4 were expressed in cell lines and tumour samples and CXCR4-1/CXCR4-2 ratio was significantly higher in tumour samples compared to cell lines and correlated with an improved EFS and OS. The results from the test panel were validated in an independent sample panel. Conclusions We identified a set of genes involved in CXCR4 signalling that may be used as a marker to predict survival and metastasis development in Ewing sarcoma.
KW - Biomarker
KW - Molecular targeted therapy
KW - Splice variant
KW - Tumour microenvironment
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U2 - 10.1016/j.ejca.2015.08.020
DO - 10.1016/j.ejca.2015.08.020
M3 - Article
C2 - 26428435
AN - SCOPUS:84969802556
VL - 51
SP - 2624
EP - 2633
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 17
ER -