Aberrant methylation of PCDH10 and RASSF1A genes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer

Charinya Pimson; Tipaya Ekalaksananan; Chamsai Pientong; Supannee Promthet; Nuntiput Putthanachote; Krittika Suwanrungruang; Surapon Wiangnon

doi:10.7717/peerj.2112

Aberrant methylation of PCDH10 and RASSF1A genes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer

PeerJ. 2016 Jun 9:4:e2112. doi: 10.7717/peerj.2112. eCollection 2016.

Authors

Charinya Pimson¹, Tipaya Ekalaksananan², Chamsai Pientong², Supannee Promthet³, Nuntiput Putthanachote³, Krittika Suwanrungruang⁴, Surapon Wiangnon⁵

Affiliations

¹ Biomedical Science Programme, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
² Department of Microbiology, Faculty of Medicine, Khon Kaen University,Khon Kaen,Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University,Khon Kaen,Thailand.
³ Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand.
⁴ Cancer Unit, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
⁵ Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Abstract

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.

Keywords: Clinicopathological factors; Gastric cancer; PCDH10; RASSF1A methylation; Survival.

Grants and funding

This work was supported by financial grants from the HPV & EBV and Carcinogenesis Research Group, and the Faculty of Medicine, Khon Kaen University, Thailand (Grant number IN58334). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.