Abstract
The mitotic checkpoint gene (CHFR) (Checkpoint with Forkhead-associated and Ring finger domains is a G2 phase/mitosis checkpoint and tumor-suppressor gene. Recent studies have reported the relationship of CHFR promoter methylation with clinicopathological significance of gastric cancer. However, the results remain unclear due to small size of sample. We pooled 15 studies including 827 gastric cancer patients and conducted a meta-analysis to investigate the clinicopathological significance of CHFR promoter methylation in gastric cancer. Our data revealed that the frequency of CHFR promoter methylation was higher in gastric cancer than in normal gastric tissue, Odd Ratio (OR) was 10.12 with 95% CI 5.17–19.79, p < 0.00001. Additionally, the rate of CHFR promoter methylation was significantly increased in high grade of gastric cancer compared to low grade, OR was 1.64 with 95% CI 1.00–2.68, p = 0.05. CHFR methylation was significantly associated with the positive lymph node metastasis, OR was 1.56 with 95% CI 1.05–2.32, p = 0.03. We concluded that CHFR could serve as a biomarker for diagnosis of gastric cancer, and a drug target for development of gene therapy in gastric cancer. CHFR promoter methylation is associated with tumor poor differentiation and lymph node metastasis.
Highlights
Gastric cancer (GC) incidence has significantly declined worldwide over the past a few decades, gastric cancer (GC) remains the fifth leading malignancy and the third most common cause of cancer-related mortality globally [1, 2]
12 out of 15 studies reported the frequency of CHFR methylation in GC and normal gastric mucosa, as demonstrated in Figure 2, the frequency of CHFR methylation was significantly elevated in GC compared with normal gastric mucosa, the pooled OR was 10.12, with 95% CI 5.17–19.79, p < 0.00001, I2 = 50% (Figure 2)
The rate of CHFR methylation in different grade of GC was compared, OR was 1.64, with 95% CI 1.00–2.68, p = 0.05, I2 = 38%, suggesting CHFR gene was more frequently methylated in high grade GC than in low grade GC (Figure 3)
Summary
Gastric cancer (GC) incidence has significantly declined worldwide over the past a few decades, GC remains the fifth leading malignancy and the third most common cause of cancer-related mortality globally [1, 2]. CHFR gene is located at chromosome 12q24.33 and contains a forkhead and a RING finger domain. It functions as a cell-cycle checkpoint molecule by delaying entry into the metaphase in response to microtubule stress. CHFR gene is silenced by promoter hypermethylation or mutated in several primary tumors such as 20% in NSCLC [4], 30% in esophageal cancer [5], and 40% in colorectal cancer (CRC) [6]. The rate of CHFR hypermethylation in GC was inconsistent and the relationship between CHFR methylation and clinicopathologic variables was unclear due to the small power of individual study.
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