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.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide [1]
The International Cancer Genome Consortium (ICGC)-LIRI-JP data set, including 203 HCC cases and 50 normal liver cases from Japan, showed that high Girders of actin filaments (Girdin) expression was closely related to poorer overall survival (OS) (HR = 1.873, 95% CI: 1.060–3.308, P=0.031; Figure 1D)
High Girdin expression was significantly correlated with poorer OS (HR = 1.781, 95% CI: 1.382–2.297, P
Summary
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide [1]. More than 840,000 new cases of HCC were diagnosed globally in 2018, resulting in approximately 700,000 deaths [2]. Surgery-dominated, comprehensive individual therapy, including chemotherapy and targeted therapy, has improved the survival of HCC patients to a certain extent, tumor recurrence and resistance to treatment remain key reasons for poor. Prognosis [3,4] This highlights the need to identify novel high-precision biomarkers to improve the early diagnosis and treatment of HCC patients. Studies have shown that Girdin possesses diverse biological functions, including as an enhancer of AKT phosphorylation and Gα-binding vesicle-associated protein [5,6,7]. We have previously demonstrated that Girdin plays a key role in the formation and function of invadopodia in HCC [8]; no study to date has explored the relationship among Girdin DNA methylation, its high expression, and immune infiltration in HCC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
