Abstract
Background and ObjectivesTo investigate the clinical value of CDH1 methylation in preoperative peritoneal washes (PPW) from gastric cancer patients.MethodsCDH1 methylation was detected by real-time methylation specific-PCR in tumor tissues and corresponding PPW from 92 gastric cancer patients, gastric mucosa from 40 chronic gastritis patients and 48 normal persons.ResultsCDH1 methylation was found in 75 of 92 (81.5%) gastric cancer tissues, which significantly correlated with size, growth pattern, differentiation, lymphatic invasion, venous invasion, invasion depth, lymph node metastasis, distant metastasis, and TNM stage of tumor (all P < 0.05), but its relationship to age, gender, tumor site, and H. pylori infection was not found (all P > 0.05). The percentage of CDH1 methylation in PPW was 48.9%, of which the Aζ value of ROC curve was 0.8 compared to that in gastric cancer tissues. Kaplan–Meier analysis showed that there was a significant difference in disease-free survival (DFS) between the patients with or without methylated CDH1 in their PPW (χ2 = 109.64, P < 0.000). Cox regression analysis revealed CDH1 methylation in PPW was an independent risk factor for gastric cancer patients, with a remarkable decrease in DFS after postoperative 30 months.ConclusionsMethylated CDH1 in PPW predicts poor prognosis for gastric cancer patients. J. Surg. Oncol. 2012; 106:765–771. © 2012 Wiley Periodicals, Inc.
Highlights
Gastric carcinoma (GC) is one of the highly prevalent malignant diseases worldwide which carries a very poor prognosis, and the 5-year survival rate is low
CDH1 methylation was not found in DNA samples of the gastric mucosa from 48 patients with chronic gastritis and 40 normal persons
It is demonstrated that CDH1 promoter 50-CpG island is methylated to varying degrees in choriocarcinoma [35], prostatic carcinoma [18,36], malignant melanoma [19], non-small cell lung cancer [20], hepatocarcinoma [21], and gastric cancer [23], of which hypermethylation is implicated in the epigenetic silencing of the CDH1 gene, leading to reduced or absent E-cadherin expression [12,13,14,15,16,17,18,19,20,21,22,23,24,25,34,35,36]
Summary
Gastric carcinoma (GC) is one of the highly prevalent malignant diseases worldwide which carries a very poor prognosis, and the 5-year survival rate is low. It has been already verified that GC was characterized by rapid deterioration, early metastasis, without much chance for radical operation and poor prognosis. Those patients without non-specific symptoms at early stage had mostly lost the opportunity of surgical therapy when gastric cancer was detected at advanced stage [2,3]. Methods: CDH1 methylation was detected by real-time methylation specific-PCR in tumor tissues and corresponding PPW from 92 gastric cancer patients, gastric mucosa from 40 chronic gastritis patients and 48 normal persons. Kaplan–Meier analysis showed that there was a significant difference in disease-free survival (DFS) between the patients with or without methylated CDH1 in their PPW (x2 1⁄4 109.64, P < 0.000).
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