J Gastric Cancer.  2013 Sep;13(3):157-163.

Disappearance of Serum Methylated p16 Indicates Longer Survival in Patients with Gastric Cancer

• Lim HK
• Park JM
• Chi KC
• Lee EJ
• Jeong EM

Abstract

PURPOSE
The aim of this study was to assess clinical correlations with postoperative alteration of p16 DNA methylation, and to clarify whether postoperative changes in the serum DNA methylation status of p16 could be used as a reliable prognostic factor for gastric cancer.
MATERIALS AND METHODS
Fifty-three consecutive gastric adenocarcinoma patients who underwent gastric resection (Chung-Ang University Hospital, Seoul, Korea) were included. DNA methylation of p16 was evaluated by methylation-specific polymerase chain reaction using serum DNA preoperatively and at the 10th postoperative day. The correlation between changes in methylation status and patients' prognosis was analyzed.
RESULTS
p16 was methylated in 79.2% of preoperative serum DNA and in 54.7% of postoperative serum DNA, respectively. Methylation in p16 disappeared more frequently in patients who underwent standard D2 lymphadenectomy compared to those who underwent modified D1+ lymphadenectomy (P=0.016). Whereas methylation of preoperative serum DNA was not correlated with survival, patients with postoperative disappearance of p16 methylation showed longer survival than those without postoperative disappearance of p16 methylation in the patients who had gastric cancer with lymph node metastasis (P=0.042).
CONCLUSIONS
Postoperative disappearance of p16 methylation could be an available prognostic factor for node-positive gastric cancer.

Keyword

Stomach neoplasms; Methylation; Genes, p16

MeSH Terms

Adenocarcinoma
DNA
DNA Methylation
Genes, p16
Humans
Lymph Node Excision
Lymph Nodes
Methylation
Neoplasm Metastasis
Polymerase Chain Reaction
Prognosis
Stomach Neoplasms
DNA

Figure

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  Fig. 1 Representative gel electrophoresis pictures demonstrating aberrant methylation in p16 for preoperative and postoperative serum DNA. M and U, the methylated and unmethylated primers, respectively. DNA from the H1299 cell line was used as positive controls for methylation. Water was used as negative control for each amplification.

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  Fig. 2 Kaplan-Meier survival curves of 53 gastric cancer patients according to the preoperative hypermethylation of p16 gene (A) and Kaplan-Meier survival curves of 42 gastric cancer patients who had preoperative p16 methylation according to the postoperative disappearance of p16 hypermethylation (B).

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  Fig. 3 Kaplan-Meier survival curves of gastric cancer patients who had preoperative p16 methylation according to the postoperative disappearance of p16 hypermethylation. (A) Seventeen early gastric cancer (EGC) patients. (B) Twenty-five advanced gastric cancer (AGC) patients. (C) Twentysix gastric cancer patients without lymph node metastasis. (D) Sixteen gastric cancer patients with lymph node metastasis.

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