1. Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China
2. Laboratory of Cancer Biology, Key Lab of Biotherapy, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China
# These authors contribute to this work equally.
Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
Keywords: CHFR, gastric cancer, methylation, diagnosis biomarker