AUTHOR=Luo YingHao , Wang Kan , Zhan Lu , Zeng Fanyue , Zheng Jie , Chen Sijing , Duan Xingbang , Ju Donghui TITLE=β3GNT9 as a prognostic biomarker in glioblastoma and its association with glioblastoma immune infiltration, migration and invasion JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1214413 DOI=10.3389/fonc.2023.1214413 ISSN=2234-943X ABSTRACT=Background

Studies have shown that the immune infiltration of tumor microenvironment is related to the prognosis of glioblastoma, which is characterized by high heterogeneity, high recurrence rate and low survival rate. To unravel the role of β1,3-N-acetylglucosaminyltransferase-9 (β3GNT9) in the progression of glioblastoma, this study identifies the value of β3GNT9 as a prognostic biomarker in glioblastoma, and investigates the relationship between β3GNT9 expression and glioblastoma immune infiltration, migration and invasion

Methods

β3GNT9 expression in glioblastoma was analyzed using the GEPIA database. The clinical features of glioblastoma were screened out from the TCGA database. The relationship between β3GNT9 expression and clinical features was analyzed. The relationship between β3GNT9 and the prognosis of glioblastoma was evaluated through univariate and multivariate COX regression analyses, and the survival analysis was conducted using the Kaplan-Meier method. GSEA was employed to predict the signaling pathway of β3GNT9 in glioblastoma. The correlation between β3GNT9 and tumor immune infiltration was analyzed using the related modules of CIBERSORT and TIMER. A172, U87MG and U251 cell lines were selected to verify β3GNT9 expression in vitro. The effects of β3GNT9 on the migration and invasion of glioblastoma were investigated through cell scratch and invasion assays.

Results

β3GNT9 expression in glioblastoma group was significantly higher than that in normal brain tissue group (P<0.05). The overall survival rate in high β3GNT9 expression group was significantly lower than that in low β3GNT9 expression group (P<0.05). Regression analyses suggested that β3GNT9, involved primarily in glucosamine degradation and extracellular matrix receptor interaction, could be an independent prognostic factor for glioblastoma. CIBERSORT and GEPIA database analyses showed that β3GNT9 was correlated with tumor infiltrating immune cells such as T follicular helper cells, activating natural killer cells, monocytes, macrophages, and eosinophils, thus affecting the immune microenvironment of glioblastoma. Cell experiments confirmed that β3GNT9 was highly expressed in A172, U87MG and U251 cell lines (P<0.05), and promoted the migration and invasion of glioblastoma (P<0.05).

Conclusion

The increased expression of β3GNT9 in glioblastoma can affect the immune microenvironment of glioblastoma and promote its migration and invasion. β3GNT9 can be used as a potential independent prognostic biomarker for patients with glioblastoma.