Cystatin M expression is reduced in gastric carcinoma and is associated with promoter hypermethylation.

Abstract

Cystatin M is a secreted inhibitor of lysosomal cysteine proteases and increasing evidences indicate that it is a novel target for epigenetic silencing during mammary tumorigenesis. Aberrant promoter methylation is a well-known mechanism that participates in cystatin M silencing in breast cancer. However, the role of cystatin M in the gastric cancer remains to be elucidated. Immunohistochemistry was used to investigate the expression of cystatin M in 60 gastric carcinomas. Hypermethylation of cystatin M promoter was evaluated by the methylation-specific PCR (MSP) method in gastric carcinomas (tumor and paired adjacent non-tumor tissues). Reverse-transcriptase PCR and BSP were also performed on gastric cancer cell lines before and after treatment with 5-aza-2'-deoxycytidine (5-Aza-dC). Lost expression of cystatin M was observed in 42 of 60 (70%) gastric carcinomas. 55% (33 of 60) of primary tumors analyzed displayed cystatin M promoter hypermethylation, indicating that this aberrant characteristic is common in gastric malignancies. Moreover, a statistically significant inverse association was found between cystatin M methylation status and expression of the cystatin M protein in tumor tissues (p=0.027). We also found that patients with cystatin M promoter methylation had a significantly shorter survival time than those without this methylation (p=0.020). These results suggest that cystatin M promoter hypermethylation is one of the molecular mechanisms that accounts for reduced cystatin M gene expression in gastric carcinomas.

• Authors: Xiaobing Chen, Xinguang Cao, Wenjie Dong, Microgene Xia, Suxia Luo, Qingxia Fan, Jing Xie
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 391 Issue 1 Pg. 1070-4 (Jan 01 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20004178 (Publication Type: Journal Article)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cystatin M

Topics

• Base Sequence
• Biomarkers, Tumor (genetics)
• Carcinoma (genetics, mortality, pathology)
• Cell Line, Tumor
• Cystatin M (genetics)
• DNA Methylation
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Molecular Sequence Data
• Prognosis
• Promoter Regions, Genetic
• Stomach Neoplasms (genetics, mortality, pathology)