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

Chen Wang,Xiaoqin Zhang,Bin Wang,Ningning Shen,Xin Li,Rong Wei,Ying Wang,Yaping Zhang,Li E,Lifang Shang,Wenxia Ma,Aiping Du,Lifang Gao

doi:10.18632/oncotarget.21962

Chen Wang, Xiaoqin Zhang + Show 11 more

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https://doi.org/10.18632/oncotarget.21962

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Journal: Oncotarget	Publication Date: Oct 23, 2017
Citations: 7	License type: cc-by

Affiliation: Second Hospital of Shanxi Medical University

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.

Highlights

Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality in the world
The aim of this study is to investigate the Clinicopathological significance of Checkpoint with Forkhead-associated and Ring finger domains (CHFR) promoter methylation in non-small cell lung cancer (NSCLC) with a meta-analysis
Scolnik and Halazonetis were the first to report the lack of CHFR gene in colorectal cancer and neuroblastoma cell lines, after loss of CHFR expression has been observed in a variety of malignancies such as colorectal cancer [12,13,14], gastric cancer [15,16,17,18], esophageal cancer [10, 19] and NSCLC [20,21,22]

Summary

Introduction

Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality in the world. Lung cancer subtypes share some genetic variations such as inactivation of tumor suppressor gene TP53, each subtype harbors its own specific genetic variations such as c-MET in ADC, fibroblast growth factor receptor 1 (FGFR1) and FGFR3 in SCC. Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a G2/M checkpoint gene that has been identified by Scolnik and Halazonetis [7]. This protein contains a forkhead and a RING finger domain, and functions as an ubiquitin ligase that ubiquitinates target proteins to direct them to the proteasome for degradation or to alter their activity [8, 9].

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