title: 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.affiliation: Department of Internal Medicine-Oncology, The First Affiliated Hospital, Zhengzhou University, People's Republic of China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.forename: Xinguang
authors.initials: X
authors.lastname: Cao
authors.forename: Wenjie
authors.initials: W
authors.lastname: Dong
authors.forename: Microgene
authors.initials: M
authors.lastname: Xia
authors.forename: Suxia
authors.initials: S
authors.lastname: Luo
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D055332:Cystatin M / Q000235:genetics*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D011379:Prognosis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D055332:Cystatin M