title: Promoter methylation of RNF180 is associated with H.pylori infection and serves as a marker for gastric cancer and atrophic gastritis.
abstract: Promoter methylation (PM) of RING-finger protein (RNF) 180 affects gastric cancer (GC) prognosis, but its association with risk of GC or atrophic gastritis (AG) is unclear. We investigated relationships between RNF180 PM and GC or AG, and the effects of Helicobactor pylori (H.pylori) infection on RNF180 PM. This study included 513 subjects (159 with GC, 186 with AG, and 168 healthy controls [CON]) for RNF180 PM analysis, and another 55 GC patients for RNF180 gene expression analysis. Methylation was quantified using average methylation rates (AMR), methylated CpG site counts (MSC) and hypermethylated CpG site counts (HSC). RNF180 promoter AMR and MSC increased with disease severity. Optimal cut-offs were GC + AG: AMR > 0.153, MSC > 4 or HSC > 1; GC: AMR > 0.316, MSC > 15 and HSC > 6. Hypermethylation at 5 CpG sites differed significantly between GC/AG and CON groups, and was more common in GC patients than AG and CON groups for 2 other CpG sites. The expression of RNF180 mRNA levels in tumor were significantly lower than those in non-tumor, with the same as in hypermethylation than hypomethylation group. H.pylori infection increased methylation in normal tissue or mild gastritis, and increased hypermethylation risk at 3 CpG sites in AG. In conclusion, higher AMR, MSC and HSC levels could identify AG + GC or GC. Some RNF180 promoter CpG sites could identify precancerous or early-stage GC. H.pylori affects RNF180 PM in normal tissue or mild gastritis, and increases hypermethylation in 3 CpG sites in AG.
authors.affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Sun
authors.affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Qiao-Yi
authors.initials: QY
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Cao
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Dai-Ming
authors.initials: DM
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Yong-Zhan
authors.initials: YZ
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Kai-Chun
authors.initials: KC
authors.lastname: Wu
authors.affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005757:Gastritis, Atrophic / Q000235:genetics / Q000382:microbiology*; D016481:Helicobacter Infections / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C571330:RNF180 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: CpG islands; atrophic gastritis; bisulfite genomic sequencing; gastric cancer; methylation