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Background.  Assessment of DNA methylation of specific genes is one approach to the diagnosis of cancer worldwide. Early stage detection is necessary to reduce the mortality rate of cancers, including those occurring in the stomach. For this purpose, tumor cells in circulating blood offer promising candidates for non-invasive diagnosis. Transcriptional inactivation of tumor suppressor genes, like  PCDH10  and  RASSF1A , by methylation is associated with progression of gastric cancer, and such methylation can therefore be utilized as a biomarker.   Methods.  The present research was conducted to evaluate DNA methylation in these two genes using blood samples of gastric cancer cases. Clinicopathological data were also analyzed and cumulative survival rates generated for comparison.   Results.  High frequencies of  PCDH10  and  RASSF1A  methylations in the gastric cancer group were noted (94.1% and 83.2%, respectively, as compared to 2.97% and 5.45% in 202 matched controls). Most patients (53.4%) were in severe stage of the disease, with a median survival time of 8.4 months after diagnosis. Likewise, the patients with metastases, or  RASSF1A  and  PCDH10  methylations, had median survival times of 7.3, 7.8, and 8.4 months, respectively. A Kaplan–Meier analysis showed that cumulative survival was significantly lower in those cases positive for methylation of  RASSF1A  than in their negative counterparts. Similarly, whereas almost 100% of patients positive for  PCDH10  methylation had died after five years, none of the negative cases died over this period. Notably, the methylations of  RASSF1A  and  PCDH10  were found to be higher in the late-stage patients and were also significantly correlated with metastasis and histology.   Conclusions.   PCDH10  and  RASSF1A  methylations in blood samples can serve as potential non-invasive diagnostic indicators in blood for gastric cancer. In addition to  RASSF1A  methylation, tumor stage proved to be a major prognostic factor in terms of survival rates.

Aberrant methylation ofPCDH10andRASSF1Agenes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer