title: NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population.
abstract: In order to assess whether N-Myc downstream regulated gene 4 (NDRG4) methylation was associated with the diagnosis and prognosis of gastric cancer, we measured the methylation of NDRG4 promoter and gene body regions among 110 gastric cancer patients using quantitative methods (MethyLight and pyrosequencing). Both NDRG4 promoter and gene body methylation levels were increased in tumor tissues than paired adjacent normal tissues (P < 0.001). NDRG4 gene body methylation was found to be significantly associated with age and tumor differentiation. NDRG4 promoter hypermethylation was proved to be a predictor of poor overall survival. However, opposite result was observed among The Cancer Genome Atlas (TCGA) cohort. The findings from gastric cell lines and public databases have suggested that NDRG4 methylation level was inversely associated with NDRG4 transcription level. Subsequent luciferase reporter gene assay showed that promoter CpG island but not gene body CpG island was able to upregulate gene expression. Collectively, NDRG4 promoter hypermethylation contributed to the risk of gastric cancer and predicted a poor prognosis in Chinese gastric cancer patients. Moreover, the combined methylation levels of NDRG4 promoter and gene body served as diagnostic biomarkers in gastric cancer.
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Guili
authors.initials: G
authors.lastname: Liu
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
authors.forename: Jieer
authors.initials: J
authors.lastname: Ying
authors.affiliation: Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002681:China; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; D009124:Muscle Proteins; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins
keywords: DNA methylation; N-Myc downstream regulated gene 4; diagnosis; gastric cancer; prognosis