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Open Access Research article

Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma

Hajime Tamura1, Makoto Suzuki12*, Yasumitsu Moriya1, Hidehisa Hoshino1, Tatsuro Okamoto1, Shigetoshi Yoshida1 and Ichiro Yoshino1

Author Affiliations

1 Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-Ku, Chiba 280-8670, Japan

2 Department of Thoracic Surgery, Graduate School of Medicine, Kumamoto University, 1-1-1 Honsou, Kumamoto 860-8556, Japan

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BMC Cancer 2011, 11:220  doi:10.1186/1471-2407-11-220

Published: 5 June 2011

Abstract

Background

N-methyl-D-aspartate receptors (NMDAR) act as tumor suppressors of digestive malignancies. The expression and genetic methylation patterns of NMDAR2B in non-small cell lung cancer (NSCLC) are unknown.

Methods

The relationship between gene methylation and expression of NMDAR2B was analyzed in NSCLC cell lines (N = 9) and clinical tissues (N = 216). The cell lines were studied using RT-PCR and 5-aza-2'-deoxycytidine treatment, while the clinical tissues were examined by methylation specific real-time quantitative PCR and immunohistochemistry. Retrospective investigation of patient records was used to determine the clinical significance of NMDAR2B methylation.

Results

NMDAR2B was silenced in five of the nine cell lines; 5-aza-2'-deoxycytidine treatment restored expression, and was inversely correlated with methylation. Aberrant methylation of NMDAR2B, detected in 61% (131/216) of clinical NSCLC tissues, was inversely correlated with the status of protein expression in 20 randomly examined tumors. Aberrant methylation was not associated with clinical factors such as gender, age, histological type, or TNM stage. However, aberrant methylation was an independent prognostic factor in squamous cell carcinoma cases.

Conclusions

Aberrant methylation of the NMDAR2B gene is a common event in NSCLC. The prognosis was significantly better for cases of squamous cell carcinoma in which NMDAR2B was methylated. It may have different roles in different histological types.