Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization

Abstract

Glioblastoma (GBM) is a highly malignant glioma, which has the propensity to infiltrate throughout the brain in contrast to pilocytic astrocytoma (PA) of the posterior fossa, which does not spread and can be cured by surgery. We have used Suppression Subtractive Hybridization to define markers that better delineate the molecular basis of brain invasion and distinguish these tumor groups. We have identified 106 genes expressed in PA versus GBM and 80 genes expressed in GBM versus PA. Subsequent analysis identified a subset of 20 transcripts showing a common differential expression pattern for the two groups. GBM differs from PA by the expression of five genes involved in invasion and angiogenesis: fibronectin, osteopontin, chitinase-3-like-1 (YKL-40), keratoepithelin and fibromodulin. PA differs from GBM by the expression of genes related to metabolism (apolipoprotein D), proteolysis (protease-serine-11), receptor and signal transduction (PLEKHB1 for Pleckstrin-Homology-domain-containingprotein-family-B-member-1), transcription/translation (eukaryotic-translation-elongation-factor-1-a1) processes and cell adhesion (SPOCK1 for SPARC/Osteonectin-CWCV-kazal-like-domains-proteoglycan). The expression of these genes was confirmed by real-time quantitative RT-PCR and immunohistochemistry. This study highlights the crucial role of brain invasion in GBM and identifies specific molecules involved in this process. In addition, it offers a restricted list of markers that accurately distinguish PA from GBM.

Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy

“…The adult and pediatric GBMs and pediatric LGA and JPA expressed significantly more mRNA compared with ependymomas (P < 0.05). Our results for JPA differ from a study of pilocytic astrocytoma where Suppression Subtractive Hybridization was used to identify genes differentially expressed between these two types of tumors [37]. Using this method, YKL-40 was found expressed in adult GBM but not in pediatric astrocytoma.…”

Two novel VHL targets, TGFBI (BIGH3) and its transactivator KLF10, are up-regulated in renal clear cell carcinoma and other tumors

“…TGFBI was also highly expressed in brain tumors but not in normal brain tissue suggesting that it may serve as a diagnostic marker. Since similar observations were reported by other investigators [43,44], we suggest that it is now imperative to see if TGFBI protein can be secreted by malignant brain cells into the cerebrospinal fluid and serve for early detection of brain tumors. What role(s) may TGFBI play in tumorigenesis?…”

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

“…27 YKL-40 is a secreted glycoprotein, which plays important roles in tissue remodeling, migration and angiogenesis. CHI3L1 is strongly up-regulated in GBM compared to low-grade astrocytoma 28 and to normal brain. 29,30 High YKL-40 levels in serum have been reported to be closely associated with shorter survival in various types of solid tumors, including glioblastoma, 31 suggesting that YKL-40 could be useful as a prognosticator for cancer survival.…”