Clinical role of NDRG2-based methylation status on survival pattern of glioblastoma.

OBJECTIVES: Gliobalstoma is the most common primary brain tumor in adults with an extensive genetic and transcriptional heterogeneity, still identification of the role of DNA methylation, as one of epigenetic alterations, is emerged. Authors aimed to study the clinical role of N-myc downstream-regulated gene 2 (NDRG2) -based methylation among GBM patients versus benign neurological diseases (BND), investigate its prognostic role and its relation with survival outcomes. METHODS: A total of 78 FFPE specimens were recruited as follows: GBM (n = 58) and BND (n = 20) then analyzed for NDRG2 methylation using Methyl II quantitative PCR system. The sensitivity and specificity of methylation was detected using receiver operating characteristic (ROC) curve and the relation with clinicopathological criteria for GBM and response to treatment were studied. Survival patterns; progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier analyses. RESULTS: Mean methylation NDRG2 level was significantly increased in GBM patients as compared to BND and its sensitivity and specificity were 96.55% and 95%, respectively with area under curve (AUC) equals 0.973. Among the clinical characteristic factors, mean methylation level reported significant difference with ECOG and tumor site. Survival out comes revealed that NDRG2 methylation increased with worse PFS and OS at significant level (long rank test X2 = 13.3, p < .0001; and X2 = 7.1, p = .008, respectively). CONCLUSION: Current findings highlight the importance of studying DNA methylation of NDRG2 as a key factor to understand the role of epigenetic alterations in GBM.

Aberrant methylation of APC and RARß2 genes in breast cancer patients.

Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. We aimed to identify epigenetic molecular markers in serum for early detection of breast cancer. Authors analyzed retrospectively the methylation status of RARß2 and APC genes in serum samples from 121 breast cancer patients, 79 patients with benign breast diseases, and 66 healthy volunteers using methylation-specific PCR. The methylated APC and RARß2 were significantly higher in breast cancer patients (93.4%, 95.6%) than benign (7.8%, 14.5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathological factors apart from triple negative breast cancer patients as all of them (χ(2) = 7.4, P = 0.007) reported to be methylated RARß2 genes. Both methylated genes were detected in all grades and stages. Both sensitivities and specificities of the methylated genes for breast cancer detection were superior to traditional tumor markers in detection of breast cancer, early stage, low grade tumors, and triple negative breast cancer patients. Thus methylated APC and RARß2 genes might be valuable serum-based molecular markers for early detection of breast cancer.