High-level expression of EPHB6, EFNB2, and EFNB3 is associated with low tumor stage and high TrkA expression in human neuroblastomas

被引:0
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作者
Tang, XX
Evans, AE
Zhao, HQ
Cnaan, A
London, W
Cohn, SL
Brodeur, GM
Ikegaki, N
机构
[1] Childrens Hosp Philadelphia, Div Oncol, Abramson Res Ctr, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Div Biostat, Abramson Res Ctr, Philadelphia, PA 19104 USA
[3] Univ Florida, Pediat Oncol Grp, Stat Off, Gainesville, FL 32601 USA
[4] Northwestern Univ, Dept Pediat, Chicago, IL 60614 USA
[5] Childrens Mem Hosp, Chicago, IL 60614 USA
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R73 [肿瘤学];
学科分类号
100214 ;
摘要
Neuroblastoma (NB) is a common pediatric tumor of neural crest origin that is biologically and clinically heterogeneous. EPH family receptor tyrosine kinases and ephrin ligands play fundamental roles in neurodevelopmental processes. Recently, we found that NE cell lines expressed several EPHB and EFNB transcripts, which encode EPHB subgroup receptors and ephrin-B subgroup ligands, respectively. To explore the role of EPHB receptors and ephrin-B ligands in the biology of NB, we examined the expression of EPHB and EFNB transcripts in 47 primary NE specimens. Multiple EPHB and EFNB transcripts were expressed in all of the NE tumors examined, suggesting the involvement of these transcripts in modulating the biological behavior of NE. Higher levels of EPHB6, EFNB2, and EFNB3 expression were found in low-stage tumors (stage 1, 2, and 4S) than in advanced-stage tumors (stage 3 and 4; P = 0.0013, P = 0.0048, and P = 0.027, respectively). Expression of TrkA, a well-established prognostic marker of favorable NB, was positively correlated with EPHB6, EFNB2, and EFNB3 expression (P < 0.0001, P = 0.0019, and P = 0.0001, respectively). MYCN-amplified tumors expressed lower levels of EPHB6, EFNB2, EFNB3, and TrkA transcripts compared to nonamplified tumors (P = 0.0006, P = 0.0023, P = 0.0048, and P = 0.0001, respectively). These data suggest that high-level expression of EPHB6, EFNB2, and EFNB3 is associated with favorable NE and that low-level expression of EPHB6, EFNB2, and EFNB3 correlates with aggressive MYCN-amplified NB. Thus, EPHB6, EFNB2, and EFNB3 may have biological relevance in NE. Further investigation on the biology of these genes may help provide insight into the treatment of NE.
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页码:1491 / 1496
页数:6
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