The overexpression of GPX8 is correlated with poor prognosis in GBM patients

Abstract

Glutathione peroxidase 8 (GPX8), located in the endoplasmic reticulum, is associated with poor prognosis in several cancers. However, the expression and functions of GPX8 in cancers remain unclear. The purpose of this study was to explore the expression and functions of GPX8 in glioblastoma (GBM). We obtained expression data of GPX8 by accessing the TCGA, CGGA, GEPIA, and TIMER2.0 databases and validated them using western blot and immunohistochemistry. The Kaplan–Meier overall survival curve and Cox regression model were used to evaluate the prognostic value of GPX8 in glioma patients. Gene ontology (GO) and function enrichment analysis were used to investigate the potential function of GPX8 in GBM. Correlation analysis was used to clarify the role of GPX8 in proneural–mesenchymal transition (PMT). We studied the correlation between GPX8 expression and GBM immune infiltration by accessing cBioPortal and TIMER2.0 databases. Here, we demonstrated that GPX8 was significantly upregulated in GBM, and was associated with IDH-wildtype and mesenchymal subtype with poor prognosis. Survival analysis results indicated that GPX8 is an independent prognostic factor for overall survival (OS) in all WHO-grade glioma patients. Through the functional studies, we found that high expression of GPX8 correlated with mesenchymal signature and negatively correlated with proneural signature, indicating that GPX8 might promote PMT in GBM. Finally, based on correlation analysis, we found that the expression of GPX8 was associated with immune infiltration and the IL1/MYD88/IRAK/NF-κB pathway in GBM. Our results show that GPX8 is a key factor affecting the prognosis of GBM patients, and its targeting has the potential to provide a novel therapeutic approach.

ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM

“…The PMT occurs in gliomas, similar to the EMT process, and is considered to be an important mechanism for promoting metastatic 35 , 47 , 48 . The results of our study confirm that ALKBH5 contributes to formation of the MES phenotype and promotes PMT in GBM, which is consistent with the previous study that ALKBH5 can affect the malignant progression of GBM 49 . In addition, we verified that proline synthesis promoted proliferation and PMT in GBM cells.…”

Hypoxia‐related THBD+ macrophages as a prognostic factor in glioma: Construction of a powerful risk model

“…Notably, EMP3, RGS16, PLAU, TAGLN2, STEAP3, CDHR1, OSMR, SERPINH1, PDPN, CHI3L1, ABCC3, SERPINE1, SOCS1, GPX8, GPNMB, CLEC5A, FOSL2, ICAM1, PRF1 and ITPRIP serve as prognostic markers for gliomas. 9 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 Among them, RGS16, CLEC5A and TAGLN2 are key regulatory factors that promote glioma progression by activating the PI3K‐AKT pathway in gliomas. 53 , 54 , 55 , 56 Additionally, upregulated STEAP3 in gliomas facilitates tumour cell migration and invasion and is significantly associated with immune‐infiltrating cells, including macrophages and neutrophils, particularly M2 macrophages.…”

“…Many of these genes have demonstrated associations with the prognosis or progression of gliomas. Notably, EMP3, RGS16, PLAU, TAGLN2, STEAP3, CDHR1, OSMR, SERPINH1, PDPN, CHI3L1, ABCC3, SERPINE1, SOCS1, GPX8, GPNMB, CLEC5A, FOSL2, ICAM1, PRF1 and ITPRIP serve as prognostic markers for gliomas 9,41–52 . Among them, RGS16, CLEC5A and TAGLN2 are key regulatory factors that promote glioma progression by activating the PI3K‐AKT pathway in gliomas 53–56 .…”

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

“…The high expression of GPX8 is associated with MES features and is negatively correlated with anterior PN features, thus suggesting that GPX8 may promote PMT in GBM. Correlation analysis has shown that GPX8 expression modulation is associated with the IL1-MYD88-IRAK-NF-κB pathway and immune infiltration in GBM 110 . Furthermore, the TGF-β-induced CLDN4/TNF-α/NF-κB signaling axis plays a key role in EMT in gliomas 111 .…”