A promoter methylation pattern in the N-methyl-D-aspartate receptor 2B gene predicts poor prognosis in esophageal squamous cell carcinoma.
OBJECTIVE
To investigate whether the promoter methylation pattern in N-methyl-d-aspartate receptor 2B (NMDAR2B) is correlated with clinical features of human esophageal squamous cell carcinoma (ESCC), the methylation status of the gene was examined at three different sites (P1, P2, and P3) where two CpG islands reside within 1 kb upstream of the transcription start site.


METHODS
Three independent modalities for methylation analysis (bisulfite sequencing, combined bisulfite restriction analysis, and TaqMan methylation-specific PCR) were done to analyze total 67 ESCC tissues that included 43 primary tumors with well-characterized clinicopathologic variables including patient outcome.


RESULTS
Using an optimized cutoff value based on quantitative methylation-specific PCR, we found that patients with higher NMDAR2B methylation ratio in the proximal region (P1) showed a worse 5-year disease-specific survival rate than those without NMDAR2B methylation (P < 0.006). A significant correlation was also seen between NMDAR2B promoter methylation and the presence of vascular permeation (P = 0.03).


CONCLUSIONS
NMDAR2B promoter methylation could be a clinically applicable marker in ESCC.
Kim
Myoung Sook
MS
Department of Otolaryngology, Head and Neck Cancer Research Division, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21231, USA.
Yamashita
Keishi
K
Chae
Young Kwang
YK
Tokumaru
Yutaka
Y
Chang
Xiaofei
X
Zahurak
Marianna
M
Osada
Motonobu
M
Park
Hannah Lui
HL
Chuang
Alice
A
Califano
Joseph A
JA
Sidransky
David
D
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate