Cheng Zhang1,2, Yang Ke1, Xuefen Lei3, Xin Liu4, Hai Li5, Runjiao Shi3, Lin Wang1. 1. Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. 2. Department of Hepatobiliary Surgery, the Sixth People's Hospital of Chengdu, Chengdu 610051, China. 3. Department of Medical Oncology, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. 4. Department of Dermatology, the Second Affiliated Hospital of Chengdu Medical College, Chengdu 610051, China. 5. School of Medicine, Kunming University, Kunming 650214, China.
Abstract
OBJECTIVE: The aim of the present study was to explore the relationship among Girdin DNA methylation, its high expression, and immune infiltration in human hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases were used to compare Girdin mRNA expression between HCC tissues and normal tissues, and determine the relationship between Girdin expression and HCC prognosis. TCGA database was also used to analyze the expression of Girdin and its methylation status, as well as the relationship between Girdin DNA methylation and HCC prognosis. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the correlation between Girdin expression and HCC immune infiltration. RESULTS: Girdin expression was elevated in HCC tissues compared with that in normal tissues. The degree of methylation at cg03188526, a CpG site in the Girdin gene body, was positively correlated with Girdin mRNA expression, while high Girdin expression and cg03188526 hypermethylation were both correlated with poor HCC prognosis. Additionally, HCC tissue with high Girdin expression exhibited abundant immune infiltration, and the high Girdin expression was associated with a worse prognosis in macrophage-enriched HCC specimens. CONCLUSION: Our findings indicated that Girdin likely functions as an oncogene in HCC and that hypermethylation at cg03188526 in the Girdin gene body may explain the high Girdin expression levels in HCC tissue. Furthermore, we report for the first time that the adverse effects of high Girdin expression in HCC patients may be partially mediated by tumor macrophage infiltration.
OBJECTIVE: The aim of the present study was to explore the relationship among Girdin DNA methylation, its high expression, and immune infiltration in human hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases were used to compare Girdin mRNA expression between HCC tissues and normal tissues, and determine the relationship between Girdin expression and HCC prognosis. TCGA database was also used to analyze the expression of Girdin and its methylation status, as well as the relationship between Girdin DNA methylation and HCC prognosis. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the correlation between Girdin expression and HCC immune infiltration. RESULTS: Girdin expression was elevated in HCC tissues compared with that in normal tissues. The degree of methylation at cg03188526, a CpG site in the Girdin gene body, was positively correlated with Girdin mRNA expression, while high Girdin expression and cg03188526 hypermethylation were both correlated with poor HCC prognosis. Additionally, HCC tissue with high Girdin expression exhibited abundant immune infiltration, and the high Girdin expression was associated with a worse prognosis in macrophage-enriched HCC specimens. CONCLUSION: Our findings indicated that Girdin likely functions as an oncogene in HCC and that hypermethylation at cg03188526 in the Girdin gene body may explain the high Girdin expression levels in HCC tissue. Furthermore, we report for the first time that the adverse effects of high Girdin expression in HCC patients may be partially mediated by tumor macrophage infiltration.
Authors: Li Yu; Yifan Sun; Jingjing Li; Yan Wang; Yuxing Zhu; Yong Shi; Xiaojun Fan; Jianda Zhou; Ying Bao; Jie Xiao; Ke Cao; Peiguo Cao Journal: J Exp Clin Cancer Res Date: 2017-08-15