Anti-EMP3 (aa 25-68) polyclonal antibody

Background/Aim: Understanding of the molecular events associated with progression and survival differences in patients with lower-grade gliomas (LGGs) is still unclear. The comparison of findings across studies using different datasets and methods is essential for a new molecular-based classification system. The aim of the study was to identify biomarkers for prognostic classification of patients with LGGs, and furthermore to lay a foundation for future development of targeted therapies for LGGs. Patients and Methods: Using information-theoretic and statistical approaches, we analyzed mRNA expression data for 18,413 genes from LGG samples in order to identify candidate biomarkers for survival. The candidate genes were then evaluated for their potential as prognostic biomarkers using multivariable Cox regression analyses that adjusted for the effects of age and grade. Results: WEE1, EMP3, E2F7, CD58 and NSUN7 genes were identified as candidate biomarkers of LGGs and their high expression was associated with significantly shorter survival. The hazard ratios for mortality were 5.02 (95% CI=3 .40-7 .40) for WEE1, 5.45 (95% CI=3 .63-8.18) for EMP3, 4.49 (95% CI=3 .03-6 .66) for E2F7, 4.77 (95% CI=3 .22-7.06) for CD58 and 4.38 (95% CI=2 .97-6 .47) for NSUN7. In addition, the expression pattern of these genes, associated with shorter survival in LGGs, was also observed in glioblastoma multiforme. Conclusion: Identification of genes associated with poor outcomes will provide insights into novel biological mechanisms that may lead to improvement in progression and survival for patients with LGGs.

The CpG island methylator phenotype is strongly associated with poor survival in neuroblastomas. Neuroblastomas with the CpG island methylator phenotype include almost all neuroblastomas with MYCN amplification, and, even among neuroblastomas without MYCN amplification, have worse prognosis. At the same time, methylation of individual tumor-suppressor genes is also reported to be associated with poor survival. The purpose of this study was to compare the prognostic power of the CpG island methylator phenotype with that of methylation of individual genes. Methylation-specific polymerase chain reaction was performed for five individual genes (CASP8, EMP3, HOXA9, NR1I2 and CD44) in 140 Japanese and 152 German neuroblastomas. KaplanMeier analysis and log-rank tests were conducted to compare the survival between groups defined by methylation status. Among the five individual genes, only CASP8 methylation had a significant association with poor overall survival both in Japanese (hazard ratio 3.1; 95 confidence interval 1.56.4; P 0.002) and German (hazard ratio 4.8; 95 confidence interval 2.111; P 0.0002) neuroblastomas. HOXA9 and NR1I2 methylation were associated with poor survival only in German neuroblastomas. On the other hand, the CpG island methylator phenotype had a strong and consistent association in Japanese (hazard ratio 22; 95 confidence interval 5.393; P 1.5 10(5)) and German (hazard ratio 9.5; 95 confidence interval 3.228; P 4.7 10(5)) neuroblastomas. The CpG island methylator phenotype is likely to have stronger prognostic power than methylation of individual genes in neuroblastomas.