ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Large-scale characterization of DNA methylation changes in human gastric carcinomas with and without metastasis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 91 citations in OpenAlex.
- Trial
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- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- Gene body methylation in cancer: molecular mechanisms and clinical applications.Clinical epigenetics · 2022Review
- The Kv10.1 Channel: A Promising Target in Cancer.International journal of molecular sciences · 2022Review
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- SOX14 hypermethylation as a tumour biomarker in cervical cancer.BMC cancer · 2021Article
- Serum response factor-cofactor interactions and their implications in disease.The FEBS journal · 2021Review
- Evaluation of the Diagnostic Potential of Candidate Hypermethylated Genes in Epithelial Ovarian Cancer in North Indian Population.Frontiers in molecular biosciences · 2021Article
- Article
- Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer.PLoS genetics · 2020Article
- Impact ofWorld journal of gastroenterology · 2020Article
- Regulation of SRF protein stability by an autophagy-dependent pathway.Biochemical and biophysical research communications · 2020Article
- SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner.Cancer management and research · 2020Article
- A panel of DNA methylated markers predicts metastasis of pNBritish journal of cancer · 2019Observational
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMetastasis is the leading cause of death for gastric carcinoma. An epigenetic biomarker panel for predicting gastric carcinoma metastasis could have significant clinical impact on the care of patients with gastric carcinoma. The main purpose of this study is to characterize the methylation differences between gastric carcinomas with and without metastasis. EXPERIMENTAL
designGenome-wide DNA methylation profiles between 4 metastatic and 4 nonmetastatic gastric carcinomas and their surgical margins (SM) were analyzed using methylated-CpG island amplification with microarray. The methylation states of 73 candidate genes were further analyzed in patients with gastric carcinoma in a discovery cohort (n=108) using denatured high performance liquid chromatography, bisulfite-sequencing, and MethyLight. The predictive values of potential metastasis-methylation biomarkers were validated in cohorts of patients with gastric carcinoma in China (n=330), Japan (n=129), and Korea (n=153).
resultsThe gastric carcinoma genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared with SMs. Significant differential methylation was validated in the CpG islands of 15 genes (P<0.05) and confirmed using bisulfite sequencing. These genes included BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Methylation changes of GFRA1, SRF, and ZNF382 resulted in up- or downregulation of their transcription. Most importantly, the prevalence of GFRA1, SRF, and ZNF382 methylation alterations was consistently and coordinately associated with gastric carcinoma metastasis and the patients' overall survival throughout discovery and validation cohorts in China, Japan, and Korea.
conclusionMethylation changes of GFRA1, SRF, and ZNF382 may be a potential biomarker set for prediction of gastric carcinoma metastasis.
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