Age-Dependent Association between Protein Expression of the Embryonic Stem Cell Marker Cripto-1 and Survival of Glioblastoma Patients.
Exploring the re-emergence of embryonic signaling pathways may reveal important information for cancer biology. Nodal is a transforming growth factor-β (TGF-β)-related morphogen that plays a critical role during embryonic development. Nodal signaling is regulated by the Cripto-1 co-receptor and another TGF-β member, Lefty. Although these molecules are poorly detected in differentiated tissues, they have been found in different human cancers. Poor prognosis of glioblastomas justifies the search for novel signaling pathways that can be exploited as potential therapeutic targets. Because our intracranial glioblastoma rat xenograft model has revealed importance of gene ontology categories related to development and differentiation, we hypothesized that increased activity of Nodal signaling could be found in glioblastomas. We examined the gene expressions of Nodal, Cripto-1, and Lefty in microarrays of invasive and angiogenic xenograft samples developed from four patients with glioblastoma. Protein expression was evaluated by immunohistochemistry in 199 primary glioblastomas, and expression levels were analyzed for detection of correlations with available clinical information. Gene expression of Nodal, Lefty, and Cripto-1 was detected in the glioblastoma xenografts. Most patient samples showed significant levels of Cripto-1 detected by immunohistochemistry, whereas only weak to moderate levels were detected for Nodal and Lefty. Most importantly, the higher Cripto-1 scores were associated with shorter survival in a subset of younger patients. These findings suggest for the first time that Cripto-1, an important molecule in developmental biology, may represent a novel prognostic marker and therapeutic target in categories of younger patients with glioblastoma.
NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Bergen, Norway.
Berit B
BB
Tysnes
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Hege A
HA
Satran
Department of Pathology, Haukeland University Hospital, Bergen, Norway ; The Gade Institute, University of Bergen, Bergen, Norway.
Sverre J
SJ
Mork
Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
Naira V
NV
Margaryan
Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway ; Department of Public Health and Primary Care, University of Bergen, Bergen, Norway.
Geir E
GE
Eide
Computational Biology Unit, Uni Computing, Uni Research AS, Bergen, Norway.
Kjell
K
Petersen
Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
Luigi
L
Strizzi
Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
Mary J C
MJ
Hendrix