Detection of Vimentin Methylation in the Serum of Patients with Gastric Cancer
2012
Aim: Detection of gastric cancer using serum assay of vimentin methylation. Methods: A quantitative methylation- specific polymerase chain reaction assay was used to detect vimentin gene (VIM) methylation in the serum of 71 patients with gastric cancer. Results: Mean VIM methylation in cancer patients (0.304±0.558) was significantly higher than that in healthy donors (0.011±0.015, p=0.018). The sensitivity of VIM methylation (33.8%) was similar to the one of carbohydrate antigen 19-9 (CA19-9) (25.4%), higher than the one of carcinoembryonic antigen (CEA) (12.7%), and significantly higher than the sensitivity of both markers for patients with stage I and IV disease (p=0.010 and 0.044, respectively). At all stages, the sensitivity of a combination of markers was higher than the sensitivity of any in isolation marker and was similar for stages I, II and III, reaching 76.9% for stage IV disease. Conclusion: VIM methylation may represent a useful marker for the detection of tumor DNA in the serum of patients with gastric cancer. Circulating DNA has been detected in the serum of cancer patients (1, 2). As a result, there have been many attempts to design an assay for the early detection of tumor-related aberrant DNA in the serum of patients with various malignancies (3, 4). In particular, we have detected tumor- specific DNA in the serum of patients with various types of cancer by using a mismatch ligation assay for KRAS and mitochondrial DNA mutations (5-8). Promoter methylation has recently been established as an important mechanism for inactivating gene transcription. Several genes, including p16 (9), p14 (10), helicase-like transcription factor (HLTF) (11), suppressor of cytokine signaling-1 (SOCS-1) (12), and cadherin 13 (CDH13) (13), exhibit promoter hypermethylation associated with a loss of gene expression in digestive tract cancer. Therefore, the presence of epigenetic methylation may represent a useful molecular target for the detection of tumor DNA. The methylation status of p16 in colorectal cancer was previously examined using methylation-specific PCR (MSP) (14). We observed that DNA from 44 out of 94 tumors (47%) displayed abnormal promoter methylation of p16. Subsequently, we found that 13 out of 44 patients (30%) with p16 promoter methylation of tumor DNA also demonstrated abnormal methylation of serum DNA. Thus, we aimed to develop a molecular biological technique to detect methylation of serum DNA. The vimentin gene (VIM), usually activated in mesenchymal cells, was recently shown to be highly methylated in colorectal carcinoma (15). Indeed, VIM gene methylation was detected in 53%-84% of colorectal carcinomas (16-18). In addition, we detected aberrant methylation of VIM in 14 out of 37 primary gastric carcinomas (38%) (19). Therefore, gastric cancer might be detected and monitored by analyzing VIM methylation in clinical samples, such as serum and stool samples (20). In the present study, we aimed to detect VIM methylation in the serum of patients with gastric cancer.
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