4.6 Article

Aberrant methylation of PCDH10 and RASSFIA genes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer

Journal

PEERJ
Volume 4, Issue -, Pages -

Publisher

PEERJ INC
DOI: 10.7717/peerj.2112

Keywords

Gastric cancer; PCDH10; RASSFIA methylation; Survival; Clinicopathological factors

Funding

  1. HPV & EBV and Carcinogenesis Research Group
  2. Faculty of Medicine, Khon Kaen University, Thailand [IN58334]

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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 RASSFIA, by methylation is associated with progression of gastric cancer, and such methylation can therefore be utilized as a bionlarker. 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 RASSFIA 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 of 7 metastases, or RASSFIA and PCDH10 methylation, had median survival times of 7.3, 7.8 and 8.4 months, respectively. A Kaplan-Meier analysis showed that cumuiative survival was significantly lower in those cases positive for methylation of RASSFIA 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 RASSFIA and PCDH10 were found to be higher in the late-stage patients land were also significantly correlated with metastasis and histology. Conclusions. PCDH10 and RASSFIA methylations in blood samples can serve as potential non-invasive diagnostic indicators in blood for gastric cancer. In addition to RASSFIA methylation, tumor stage proved to be a major prognostic factor in terms of survival rates.

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