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CHFR启动子高甲基化与胃癌相关,并在胃癌发生过程中发挥保护作用。

CHFR Promoter Hypermethylation Is Associated with Gastric Cancer and Plays a Protective Role in Gastric Cancer Process.

作者信息

Dai Dongjun, Zhou Bingluo, Xu Wenxia, Jin Hongchuan, Wang Xian

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.

Laboratory of Cancer Biology, Key Lab of Biotherapy, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.

出版信息

J Cancer. 2019 Jan 29;10(4):949-956. doi: 10.7150/jca.27224. eCollection 2019.

Abstract

: Chromosomally unstable tumors account for 50% of gastric cancer. CHFR plays a role in controlling chromosomal instability and its inactivation will eventually lead to tumorigenesis. In addition to genetic deletion, DNA methylation could silence the expression of many cancer-related genes including CHFR. Its methylation was found to be associated with the initiation and progression of gastric cancer. : We performed a meta-analysis involving methylation analyses of CHFR promoter in gastric cancer. Nineteen studies with 1,249 tumor tissues and 745 normal tissues had been included in current study. : We found that CHFR methylation was significantly higher in gastric cancer (studies numbers = 15, cases/controls = 862/745, odds ratio (OR) = 7.46, 95% confidence index (95% CI) = 4.99-11.14). Methylation array data was also obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas network (TCGA). There were 7 out of 13 CHFR methylation probes target to the same CpG island region (hg19, 131973620-131975130) showed the CHFR methylation was higher in gastric cancers than normal controls. Eight probes showed CHFR promoter hypermethylation was associated with longer overall survival of gastric cancer patients (Hazard Ratio < 1). : The CHFR promoter hypermethylation was associated with gastric cancer and played a protective role in gastric cancer process. Its methylation could be a potential biomarker for the diagnosis and prognosis of gastric cancer.

摘要

染色体不稳定的肿瘤占胃癌的50%。CHFR在控制染色体不稳定方面发挥作用,其失活最终会导致肿瘤发生。除了基因缺失外,DNA甲基化可使包括CHFR在内的许多癌症相关基因的表达沉默。发现其甲基化与胃癌的发生和进展有关。

我们进行了一项荟萃分析,涉及胃癌中CHFR启动子的甲基化分析。本研究纳入了19项研究,共1249个肿瘤组织和745个正常组织。

我们发现,胃癌中CHFR甲基化显著更高(研究数量=15,病例/对照=862/745,比值比(OR)=7.46,95%置信指数(95%CI)=4.99-11.14)。甲基化阵列数据也从基因表达综合数据库(GEO)和癌症基因组图谱网络(TCGA)获得。13个CHFR甲基化探针中有7个靶向同一CpG岛区域(hg19,131973620-131975130),结果显示胃癌中的CHFR甲基化高于正常对照。8个探针显示CHFR启动子高甲基化与胃癌患者更长的总生存期相关(风险比<1)。

CHFR启动子高甲基化与胃癌相关,并在胃癌进程中起保护作用。其甲基化可能是胃癌诊断和预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0798/6400794/14098cac2d5b/jcav10p0949g001.jpg

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