Shouming Wu1, Duoguang Wu2, Yingpeng Pan1, Hua Liu1, Zhongfan Shao1, Minghui Wang3. 1. Department of Thoracic Surgery, The First People's Hospital of LanYunGang, LianYunGang, 222002, Jiangsu Province, PR China. 2. Department of Cardiothoracic Surgery, Sun Yet-Sen Memoral Hospital Sun Yet-Sen University, Guangzhou, 510000, Guangdong Province, PR China. 3. Department of Cardiothoracic Surgery, Sun Yet-Sen Memoral Hospital Sun Yet-Sen University, Guangzhou, 510000, Guangdong Province, PR China. Electronic address: wangminghui_dr@163.com.
Abstract
OBJECTIVE: Recently, accumulated evidence indicates that the enhancer of zeste homologue 2 (EZH2) is highly expressed in a wide range of cancer types, including NSCLC. The downstream genes regulated by EZH2 were screened using bioinformatics analysis. This study aimed to analyse the correlation between the downstream genes of EZH2 and the prognosis of lung adenocarcinoma. METHODS: Expression and methylation data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) (https://cancergenome.nih.gov/) database, and data were categorized into EZH2 overexpression and EZH2 downregulation groups according to EZH2 expression. The genes that showed opposite trends of methylation and expression changes were screened, and the association of gene expression was calculated. Based on the String database, a protein association analysis was conducted to identify genes related to EZH2, which are referred to as EZH2 regulation candidate genes. According to gene expression (GSE27262) and methylation (GSE66836) chip data in the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) database, the genes with differential expression and methylation in lung adenocarcinoma tissues were analysed, and the trends of EZH2 regulation candidate gene expression and methylation were verified to identify the EZH2 regulation candidate genes. Subsequently, MethHC (http://methhc.mbc.nctu.edu.tw/php/index.php) and UALCAN (http://ualcan.path.uab.edu/index.html) were employed to verify changes in the expression and methylation of EZH2 downstream regulation candidate genes and to analyse the correlation between these genes and the prognosis of lung adenocarcinoma. RESULTS: Expression and methylation data of lung adenocarcinoma were downloaded from TCGA database and categorized into EZH2 overexpression and EZH2 downregulation groups according to EZH2 expression. A total of 337 genes that showed opposite trends of methylation and expression changes were obtained. The protein association analysis using the String (https://string-db.org/) database showed that 61 genes interact with EZH2 and 61 genes represent EZH2 downstream regulation candidate genes. Moreover, 222 genes obtained from GSE27262 and GSE66836 chip data were negatively correlated with methylation and expression changes, and centrosomal protein 55 (CEP55) was identified as the EZH2 downstream regulation candidate gene. CEP55 was upregulated in lung adenocarcinoma tissues and showed low methylation. According to gene expression data from TCGA database, CEP55 and EZH2 exhibit higher levels in lung adenocarcinoma tissue than in adjacent normal tissue. Finally, the survival analysis revealed that EZH2 is not associated with the prognosis of lung adenocarcinoma, while CEP55 is related to lung adenocarcinoma prognosis. CONCLUSION: Taken together, these results indicate that changes in EZH2 expression lead to changes in CEP55 expression in lung adenocarcinoma, and these changes are associated with its prognosis.
OBJECTIVE: Recently, accumulated evidence indicates that the enhancer of zeste homologue 2 (EZH2) is highly expressed in a wide range of cancer types, including NSCLC. The downstream genes regulated by EZH2 were screened using bioinformatics analysis. This study aimed to analyse the correlation between the downstream genes of EZH2 and the prognosis of lung adenocarcinoma. METHODS: Expression and methylation data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) (https://cancergenome.nih.gov/) database, and data were categorized into EZH2 overexpression and EZH2 downregulation groups according to EZH2 expression. The genes that showed opposite trends of methylation and expression changes were screened, and the association of gene expression was calculated. Based on the String database, a protein association analysis was conducted to identify genes related to EZH2, which are referred to as EZH2 regulation candidate genes. According to gene expression (GSE27262) and methylation (GSE66836) chip data in the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) database, the genes with differential expression and methylation in lung adenocarcinoma tissues were analysed, and the trends of EZH2 regulation candidate gene expression and methylation were verified to identify the EZH2 regulation candidate genes. Subsequently, MethHC (http://methhc.mbc.nctu.edu.tw/php/index.php) and UALCAN (http://ualcan.path.uab.edu/index.html) were employed to verify changes in the expression and methylation of EZH2 downstream regulation candidate genes and to analyse the correlation between these genes and the prognosis of lung adenocarcinoma. RESULTS: Expression and methylation data of lung adenocarcinoma were downloaded from TCGA database and categorized into EZH2 overexpression and EZH2 downregulation groups according to EZH2 expression. A total of 337 genes that showed opposite trends of methylation and expression changes were obtained. The protein association analysis using the String (https://string-db.org/) database showed that 61 genes interact with EZH2 and 61 genes represent EZH2 downstream regulation candidate genes. Moreover, 222 genes obtained from GSE27262 and GSE66836 chip data were negatively correlated with methylation and expression changes, and centrosomal protein 55 (CEP55) was identified as the EZH2 downstream regulation candidate gene. CEP55 was upregulated in lung adenocarcinoma tissues and showed low methylation. According to gene expression data from TCGA database, CEP55 and EZH2 exhibit higher levels in lung adenocarcinoma tissue than in adjacent normal tissue. Finally, the survival analysis revealed that EZH2 is not associated with the prognosis of lung adenocarcinoma, while CEP55 is related to lung adenocarcinoma prognosis. CONCLUSION: Taken together, these results indicate that changes in EZH2 expression lead to changes in CEP55 expression in lung adenocarcinoma, and these changes are associated with its prognosis.
Authors: Thomas A Sellers; Ozlen Saglam; Brett M Reid; Shraddha Vyas; Zhihua Chen; Ann Chen; Peter A Kanetsky; Jennifer B Permuth Journal: BMC Cancer Date: 2021-06-17 Impact factor: 4.430