Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

SRF methylation in myofibroblasts predicts less metastasis of non-cardiac gastric carcinomas in China, Japan, and Korea (#72)

Zhaojun Liu 1 , Chen Yang 1 , Jiafu Ji 1 , Wooho Kim 2 , Toshikazu Ushijima 3 , Dajun Deng 1
  1. Peking University Cancer Hospital and Institute, Beijing, China
  2. Pathology, Seoul National University College of Medicine, Seoul, Korea
  3. Carcinogenesis, National Cancer Center Research Institute, Tokyo, Japan

[Background & Aims] SRF promotes growth and metastasis of cancer cells. The aim is to determine whether SRF is inactivated by methylation of CpG islands and can be used as a biomarker to predict metastasis of gastric carcinoma (GC).
[Methods] 356 Chinese, 78 Japanese, and 152 Korean GC patients followed up for at least 3 years were included in the present study. Methylation status of SRF CpG islands in GC and the corresponding surgical margin (SM) samples was determined with DHPLC, MethyLight, and bisulfite sequencing. Myofibroblasts were identified with aSMA-immunostaining. Relationships between SRF methylation and GC metastasis and patients’ overall survival were analyzed.
[Results] Methylated-CpG cluster was mainly characterized within the SRF exon-1 in myofibroblasts in GC or SM. Proportion of the methylated SRF inversely correlated with its transcription activity (P=0.021). More SRF methylation-positive SM samples were seen in non-metastatic-GC patients than metastatic-GC patients in the training cohort (n=199), and consistently confirmed in the testing cohort in China (n=157) and two independent validation cohorts in Japan and Korea, respectively. Moreover, SRF methylation-positive patients with non-cardiac GC had longer overall survival than SRF methylation-negative cases not only in the training cohort [multivariate analysis, hazard ratio=0.479 (P=0.023)], but also in the testing and validation cohorts among non-cardiac GC patients from China [0.469 (P=0.016)], Japan [0.547 (P=0.045)], and Korea [0.461 (P=0.031)]. The protective effect of SRF methylation on the followup- metastasis was prospectively observed among 144 baseline-non-metastatic-GC patients (P=0.045).
[Conclusion] DNA methylation inactivates SRF expression in stromal myofibroblasts and is a useful predictor of metastasis and overall survival of non-cardiac GC patients.