Clinicopathological significance of CHFR methylation in non-small cell lung cancer: a systematic review and meta-analysis

Abstract

Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a G2/M checkpoint and tumor-suppressor gene. Recent publications showed the correlation of CHFR promoter methylation with clinicopathological significance of non-small cell lung cancer (NSCLC), however, the results remain inconsistent. The aim of this study is to investigate the Clinicopathological significance of CHFR promoter methylation in NSCLC with a meta-analysis. A total of nine studies were included in the meta-analysis that 816 patients were involved. Our data indicated that the frequency of CHFR promoter methylation was higher in NSCLC than in normal lung tissue, Odd Ratios (OR) was 9.92 with 95% corresponding confidence interval (CI) 2.17–45.23, p = 0.003. Further subgroup analysis revealed that CHFR promoter was more frequently methylated in squamous cell carcinoma (SCC) than in adenocarcinoma (ADC), OR was 4.46 with 95% CI 1.65–12.05, p = 0.003, suggesting the mechanism of SCC pathogenesis is different from ADC. Notably, CHFR promoter methylation was correlated with smoking behavior in NSCLC. In conclusion, CHFR could be a biomarker for diagnosis of NSCLC, and a promising drug target for development of gene therapy in SCC. CHFR promoter methylation is potentially associated with poor overall survival, additional studies need to be carried out for confirmation in future.

A high-throughput test enables specific detection of hepatocellular carcinoma

“…Indeed, the “HCC-detect” CpGs are associated with genes involved in cell cycle regulatory events, EMT transition and angiogenesis. CHFR encodes a cell cycle (G2/M) checkpoint, which was suggested to be a tumor suppressor gene 28 ; methylation of CHFR was associated with noninvasive colorectal cancer 29 , esophageal carcinoma 30 , hepatocellular carcinoma 31 , higher grade gastric cancer 32 and non-small cell lung carcinoma 33 . Vasohibin 2 (VASH2 ) gene was implicated in angiogenesis in invasive tumors 34 and was previously shown to be methylated in HCC 35 .…”

CHFR promotes metastasis of human gastric carcinoma by activating AKT and ERK via NRF2- ROS axis

“…As a well-known negative regulator of cell cycle progression, CHFR was regarded as a tumor suppressor gene and hypermethylation in CHFR gene promoter were frequently observed in multiple cancer types, such as colorectal cancer and gastric cancer [8,11]. The methylation level of CHFR has also been proved as a biomarker for predict the prognosis in several cancers [20,21]. However, some studies also found that lower CHFR expression was independently associated with unfavorable prognosis in acute myeloid malignances [22,23].…”

epiLiver a novel tumor specific, high throughput and cost-effective blood test for specific detection of liver cancer (HCC)

“…Indeed, the "HCC-detect" CGs are associated with genes involved in cell cycle regulatory events, EMT transition and angiogenesis. CHFR encodes a cell cycle (G2/M) checkpoint, which was suggested to be a tumor suppressor gene [26]; methylation of CHFR was associated with noninvasive colorectal cancer [27], esophageal carcinoma [28], hepatocellular carcinoma [29], higher grade gastric cancer [30] and non-small cell lung carcinoma [31]. Vasohibin 2 (VASH2) gene was implicated in angiogenesis in invasive tumors [32] and was previously shown to be methylated in HCC [33].…”