In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5344-5344
Kurzfassung:
Glioblastoma multiforme (GBM) is a poorly treated human brain cancer with few established clinically useful molecular prognostic markers. GBM gene expression and microRNA profiling recently revealed developmental subtypes that potentially correlates with prognosis and treatment response. However, the clinically significant subset of glioblastoma stem-like cells (GSC) still lacks detailed molecular characterization and correlation to patient survival. We report that molecular classification of patient-derived GSCs using neural lineage markers show association with differential xenograft invasiveness, and also demonstrate significant correlation to survival in both the mouse model and human patients. Immunoblot array of neural lineage markers classified five independently isolated human GSC lines into three classes exhibiting differential expression of oligodendrocyte progenitor cells (OPC), astrocyte progenitor cells (APC), and neural progenitor cells (NPC) markers. After orthotopic injection into immunodeficient mice, Ki-67 proliferative index independent xenograft infiltration was observed: class I GSCs (OPC and NPC positive) created focal lesions, class II GSCs (NPC positive) formed minimally invasive lesions, and class III GSCs (APC positive) established highly infiltrative lesions. The OPC marker, cyclic nucleotide phosphodiesterase (CNP), exhibited high expression in focal xenografts versus low expression in invasive xenografts. Differential CNP expression significantly correlated with mouse model survival, and CNP assay of a large clinically annotated human GBM tissue microarray also showed differential patient survival. Therefore, GSC molecular characterization with neural lineage markers revealed a novel and potentially useful clinical prognosis marker, and suggests clinical importance for patient-specific GSC subtyping. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5344. doi:1538-7445.AM2012-5344
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-5344
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2012
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
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