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

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.

SUBMITTER: Pimson C

PROVIDER: S-EPMC4906662 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Pimson Charinya C Ekalaksananan Tipaya T Pientong Chamsai C Promthet Supannee S Putthanachote Nuntiput N Suwanrungruang Krittika K Wiangnon Surapon S

PeerJ 20160609

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 methyla ...[more]

PMID: 27330867

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Project description:Background: The prognosis of gastric cancer (GC) patients is poor. The effect of aberrant DNA methylation on FOXF2 expression and the prognostic role of FOXF2 methylation in GC have not yet been identified. Methods: The RNA-Seq and gene methylation HM450 profile data were used for analyzing FOXF2 expression in GC and its association with methylation level. Bisulfite sequencing PCR (BSP) was performed to measure the methylation level of the FOXF2 promoter region in GC cell lines and normal GES-1 cells. The cells were treated with the demethylation reagent 5-Aza-dC, and the mRNA and protein expression levels of FOXF2 were then measured by qRT-PCR and western blot assays. The risk score system from SurvivalMeth was calculated by integrating the methylation level of the cg locus and the corresponding Cox regression coefficient. Results: FOXF2 was significantly downregulated in GC cells and tissues. On the basis of RNA-Seq and Illumina methylation 450 data, FOXF2 expression was significantly negatively correlated with the FOXF2 methylation level (Pearson's R = -0.42, p < 2.2e-16). The FOXF2 methylation level in the high FOXF2 expression group was lower than that in the low FOXF2 expression group. The BSP assay indicated that the methylation level of the FOXF2 promoter region in GC cell lines was higher than that in GES-1 cells. The qRT-PCR and western blot assay showed that FOXF2 mRNA and protein levels were increased in GC cells following treatment with 5-Aza-Dc. The methylation risk score model indicated that patients in the high risk group had poorer survival probability than those in the low risk group (HR = 1.84 (1.11-3.07) and p = 0.0068). FOXF2 also had a close transcriptional regulation network with four miRNAs and their corresponding target genes. Functional enrichment analysis of the target genes revealed that these genes were significantly related to several important signaling pathways. Conclusion: FOXF2 was downregulated due to aberrant DNA methylation in GC, and the degree of methylation in the promoter region of FOXF2 was related to the prognosis of patients. The FOXF2/miRNAs/target genes axis may play a vital biological regulation role in GC.

Dataset Information

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

Publications

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

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