Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis.
The aim of this study was to identify aberrantly expressed proteins in pediatric primitive neuroectodermal tumors (PNETs) and ependymomas. Tumor tissue of 29 PNET and 12 ependymoma patients was subjected to 2-dimensional difference gel electrophoresis. Gel analysis resulted in 79 protein spots being differentially expressed between PNETs and ependymomas (p < 0.01, fold change difference in expression >2). Three proteins, stathmin, annexin A1, and calcyphosine, were chosen for validation by immunohistochemistry. Stathmin was expressed 2.6-fold higher in PNETs than in ependymomas, and annexin A1 and calcyphosine were expressed 2.5- and 37.6-fold higher, respectively, in ependymomas. All PNETs showed strong staining for stathmin, and all ependymomas were strongly positive for annexin A1, whereas control tissues were negative. Calcyphosine immunoreactivity was observed in 59% of the ependymomas and was most profound in ependymoma tissue showing epithelial differentiation. mRNA expression levels of stathmin, annexin A1, and calcyphosine significantly correlated (Rs = 0.65 [p < 0.0001], Rs = 0.50 [p = 0.001], and Rs = 0.72 [p < 0.0001], respectively) with protein expression levels. In conclusion, using a proteome-wide approach, stathmin, annexin A1, and calcyphosine were successfully identified as tumor-specific proteins in pediatric PNETs and ependymomas. Ongoing studies are focused on characterizing the role of these proteins as tumor markers and potential drug targets in pediatric brain tumors.
de Bont
Judith M
JM
Department of Pediatric Oncology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
den Boer
Monique L
ML
Kros
Johan M
JM
Passier
Monique M C J
MM
Reddingius
Roel E
RE
Smitt
Peter A E Sillevis
PA
Luider
Theo M
TM
Pieters
Rob
R
D000293:Adolescent; D000328:Adult; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015180:Electrophoresis, Gel, Two-Dimensional; D004806:Ependymoma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D050777:Stathmin / Q000235:genetics / Q000378:metabolism
D017305:Annexin A1; D014408:Biomarkers, Tumor; C059605:CAPS protein, human; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D050777:Stathmin