Ye Zhou1, Xue-Bin Wang1, Xue-Ping Qiu1, Chen Wang1, Fang Zheng2. 1. Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei, China. 2. Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei, China. Electronic address: zhengfang@whu.edu.cn.
Abstract
AIM: Lots of studies have explored cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter methylation in hepatocellular carcinoma (HCC), but the established results were controversial. Hence, we conducted the meta-analysis to comprehensively investigate the association between CDKN2A promoter methylation and HCC risk. METHODS: A comprehensive search was implemented through searching PubMed, Web of Science and Embase. Associations of CDKN2A promoter methylation with HCC risk, clinicopathological features, and CDKN2A expression were assessed by the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Subgroup analyses and meta-regression were served for exploring the potential sources of heterogeneity. RESULTS: A total of 59 articles including 3067 cases and 2951 controls were incorporated in this meta-analysis. Overall, we observed a high CDKN2A promoter methylation rate (58.18%) in HCC and a significant association between the methylation and HCC risk (OR, 7.07; 95% CI, 5.67-8.80). Furthermore, CDKN2A promoter methylation was robustly associated with decreased mRNA (OR, 13.89; 95% CI, 5.44-35.45) and protein (OR, 48.19; 95% CI, 5.56-417.29). In addition, we found the methylation was related with HBV infection (OR, 3.31; 95% CI, 1.47-7.47), HCV infection (OR, 2.76; 95% CI, 1.80-4.23), cirrhosis status (OR, 1.57; 95% CI, 1.01-2.44) and older age (OR, 1.83; 95% CI, 1.14-2.94). CONCLUSIONS: Our results indicated that CDKN2A promoter methylation was associated with an enhancive HCC risk and played a crucial role in the process of HCC with a potential value to being a triage marker for HCC.
AIM: Lots of studies have explored cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter methylation in hepatocellular carcinoma (HCC), but the established results were controversial. Hence, we conducted the meta-analysis to comprehensively investigate the association between CDKN2A promoter methylation and HCC risk. METHODS: A comprehensive search was implemented through searching PubMed, Web of Science and Embase. Associations of CDKN2A promoter methylation with HCC risk, clinicopathological features, and CDKN2A expression were assessed by the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Subgroup analyses and meta-regression were served for exploring the potential sources of heterogeneity. RESULTS: A total of 59 articles including 3067 cases and 2951 controls were incorporated in this meta-analysis. Overall, we observed a high CDKN2A promoter methylation rate (58.18%) in HCC and a significant association between the methylation and HCC risk (OR, 7.07; 95% CI, 5.67-8.80). Furthermore, CDKN2A promoter methylation was robustly associated with decreased mRNA (OR, 13.89; 95% CI, 5.44-35.45) and protein (OR, 48.19; 95% CI, 5.56-417.29). In addition, we found the methylation was related with HBV infection (OR, 3.31; 95% CI, 1.47-7.47), HCV infection (OR, 2.76; 95% CI, 1.80-4.23), cirrhosis status (OR, 1.57; 95% CI, 1.01-2.44) and older age (OR, 1.83; 95% CI, 1.14-2.94). CONCLUSIONS: Our results indicated that CDKN2A promoter methylation was associated with an enhancive HCC risk and played a crucial role in the process of HCC with a potential value to being a triage marker for HCC.
Authors: Graziana Digiacomo; Claudia Fumarola; Silvia La Monica; Mara Bonelli; Andrea Cavazzoni; Maricla Galetti; Rita Terenziani; Kamal Eltayeb; Francesco Volta; Silvia Zoppi; Patrizia Bertolini; Gabriele Missale; Roberta Alfieri; Pier Giorgio Petronini Journal: Front Oncol Date: 2022-07-22 Impact factor: 5.738
Authors: Matteo Canale; Andrea Casadei-Gardini; Paola Ulivi; Maria Arechederra; Carmen Berasain; Pier-Luigi Lollini; Maite G Fernández-Barrena; Matías A Avila Journal: Int J Mol Sci Date: 2020-07-31 Impact factor: 5.923