Diagnostic and prognostic value of glycosyltransferase mRNA in glioblastoma multiforme patients

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary human brain tumour in adults with an average survival of 11 months. The 2-year survival is less than 10%, and only a small proportion of patients are alive at 3 years. Despite improved treatment strategies and aggressive therapy, the prognosis of GBM has changed little in past decades. Thus, any test that can reliably and rapidly diagnose the tumour and predict patient survival could be a valuable tool. Herein we report the use of quantitative real-time polymerase chain reaction (PCR) to quantify five glycosyltransferase transcripts in gliomas. Our results indicate that measuring GM1 synthase (beta-1,3 galactosyltransferase) mRNA may provide a useful method for segregating GBMs from other types of gliomas. In these studies, 97% of gliomas (36/37 tumours) below a threshold value had a diagnosis of GBM compared with 49% (52/106 tumours) above the threshold. More importantly, the increased expression of GD3 synthase mRNA in combination with decreased GalNAcT message correlated with increased survival in 79 GBM patients (proportional hazards model controlling for age, P = 0.02). These data were further corroborated by a data analysis from one of our previous studies on gangliosides of 80 GBMs, in which increased amounts of GM3 and GD3 (which accumulate in the absence of GalNAcT) correlated with a longer survival (P < 0.01). Thus, measuring GalNAcT and GD3 transcripts may provide a rapid method to assess prognosis in GBM patients. In summary, the data indicate that measuring glycosyltransferase mRNA levels by real-time PCR may be clinically useful for determining both diagnosis and prognosis in GBM patients.

Molecular Mechanisms of GD3-Induced Apoptosis in U-1242 MG Glioma Cells

“…However, in a recent study we found that increased expression of the mRNA for GD3 synthase combined with decreased expression of Gal-NAcT correlated with increased survival in patients with glioblastoma multiforme (GBM). Furthermore, combined increases in GD3 and GM3 in GBM tissues also correlated with increased survival of these patients [28]. It is possible that this prolonged survival may be at least in part due to GD3 has no effect on the expression and distribution of FADD.…”

GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells

“…PCR primers for G D3 synthase and G T3 synthase cDNA amplification were designed using Primer Premier 3.1 software (Biosoft International, Palo Alto, CA, USA). The primer sequences for G M3 synthase, G M2 /G D2 synthase, and HPRT were previously described (Garcìa-Vallero et al, 2006;Oblinger et al, 2006;Zhang et al, 2005). All the primers were synthesized by Eurogentec (Seraing, Belgium).…”

Focused microarray analysis of glyco‐gene expression in human glioblastomas

“…From these studies and several other recent reports that suggested that glycosyltransferase mRNA levels can be used as diagnostic markers for detecting metastatic neuroblastoma cells (Hoon et al 2001) in bone marrow and high grade glioblastomas (Oblinger et al 2006), a more detailed analysis of glycosyltransferase and glycosyl hydrolase gene expression in human malignant gliomas was undertaken. A focused oligonucleotide microarray containing all of the cloned human ''glyco-genes'' was constructed and used to screen a panel of primary human gliomas, normal human brain and human glioma cell lines.…”