Abstract

BackgroundAlthough many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas.MethodsWe used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells.ResultsGNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration.ConclusionsBased on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

Highlights

  • Many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and new biomarkers need to be identified

  • We examined the relationship between the expression of GNG5 in glioma tissues and the immune microenvironment using the single-sample gene set enrichment analysis to calculate the enrichment of 29 immune cell geneset signatures in each glioma sample based on data downloaded from the Chinese Glioma Genome Atlas (CGGA) database [18,19,20]

  • We used data from the CGGA database that contains a large number of glioma gene expression profiles and a vast amount of clinical information data to further analyze the relationship between GNG5 expression and the clinical features of glioma

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Summary

Introduction

Many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. GNG7 is an epigenetic silencing gene involved in the malignant progression of renal clear cell carcinoma and esophageal cancer [7, 8]; GNG4 function shows a high degree of correlation with liver cancer and colorectal cancer and is used in their diagnosis and prognosis [9, 10]; and GNG11 promotes the adhesion, migration, and invasion of gastric cancer cells [11]. The G-protein family is associated with tumor progression and may be used as potential biomarkers for the diagnosis and treatment of tumors

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