The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients

Yao, Jiawei; Chen, Xin; Liu, Zhendong; Zhang, Ruotian; Zhang, Cheng; Yang, Quan; Yao, Penglei; Jiang, Qiuyi; Wu, Jianing

doi:10.1186/s41016-021-00235-3

Cited by 7 publications

(12 citation statements)

References 22 publications

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“…It has also been reported the expression levels of GPX7 in glioma tissues were higher than those in normal brain tissues. Elevated expression levels of GPX7 led to poor prognosis of glioma patients [10]. These ndings are consistent with ours.…”

Section: Discussionsupporting

confidence: 91%

“…Glutathione peroxidase-7 (GPX7) is important in alleviation of the damage associated with ROS to body cells and is also involved in maintaining body redox homeostasis [7]. Studies have shown that the differential expressions of GPX7 are associated with some tumors, including breast cancer [3], gastric cancer [8], esophageal cancer [9], glioma [10] and hepatocellular carcinoma [ 11] among others. Although GPX7 gene expression and its transcription characteristics have been detected in various cancers, studies on GPX7 expression in cancers are limited by small sample sizes, or are focused on a single or limited number of cancers.…”

Section: Introductionmentioning

confidence: 99%

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GPX7 is Identified as a Novel Prognostic Indicator for Brain Lower Grade Glioma (LGG): Evidence from a Pan-Cancer Analysis

Zhao

Yin

Zhang

et al. 2021

Preprint

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Background: Glutathione peroxidase-7 (GPX7), a newly discovered non-selenium-containing protein with glutathione peroxidase activity, is located near the endoplasmic reticulum. Various studies have reported the involvement of GPX7 in cancer disease progression. However, the expression patterns of GPX7 and its prognostic potential have not been evaluated from a pan-cancer perspective. Moreover, the relationship between GPX7 and prognosis in Brain Lower Grade Glioma (LGG) patients remains unclear.Methods: Expression levels of GPX7 were evaluated using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA2) were used to evaluate the effect of GPX7 on clinical prognosis in TCGA tumors. Correlations between GPX7 and cancer immune infiltrates were investigated using the Tumor Immune Estimation Resource (TIMER) site and Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm. In addition, the GEPIA2 and STRING websites were used for enrichment analysis of GPX7-related genes. Finally, we constructed a prognostic Nomogram for LGG to verify the overall survival (OS) outcomes of patients.Results: GPX7 was found to be overexpressed in multiple tumors. Elevated expression levels of GPX7 were associated with poor prognosis regarding OS, disease-free survival (DFS) and progression-free survival (PFS) of LGG patients (OS Hazard ratio (HR) = 1.044, p < 0.0001; DFS HR = 1.035, p < 0.0001; PFS HR = 1.045, p < 0.0001). Concordance index (C-index) of the nomogram for LGG was 0.845 (95% CI, 0.825 to 0.865; p < 0.001). The nomogram exhibited a better predictability. In addition, GPX7 expression and the abundance of Cancer-associated fibroblasts (CAFs) were positively correlated in most cancer types. Enrichment analysis revealed that GPX7 may be involved in the glutathione derivative biosynthetic and glutathione metabolic biological processes.Conclusion: GPX7 was found to be upregulated in multiple tumors, which was correlated with poor prognosis in LGG. Therefore, GPX7 is a potential prognostic indicator for LGG. There is a strong correlation between GPX7 expression levels and glutathione metabolic pathways. GPX7 holds promise for the use of glutathione metabolism for guided therapy in cancer patients.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

GPX7 is Identified as a Novel Prognostic Indicator for Brain Lower Grade Glioma (LGG): Evidence from a Pan-Cancer Analysis

Zhao

Yin

Zhang

et al. 2021

Preprint

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“…Multiple studies have explored the relationship between GPX7 and specific tumors. 14 , 31 , 32 Our study revealed that the expression of GPX7 was elevated in multiple tumor tissues, including LGG, GBM, BRCA, ESCA, LIHC. Yao et al reported that the expression of GPX7 was higher in glioma tissue compared with normal brain tissue.…”

Section: Discussionmentioning

confidence: 69%

“…Yao et al reported that the expression of GPX7 was higher in glioma tissue compared with normal brain tissue. 32 Previous studies have shown that GPX7 has potential tumor suppressor effects in gastric cancer and esophageal adenocarcinoma. 12 , 14 , 33 Down-regulation and dysfunction of GPX7 expression in esophageal cells increase ROS level and oxidative DNA damage.…”

Section: Discussionmentioning

confidence: 99%

A Bioinformatic Analysis: The Overexpression and Prognostic Potential of GPX7 in Lower-Grade Glioma

Zhao¹,

Zhang²,

Wang³

et al. 2022

IJGM

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Purpose Glutathione peroxidase-7 ( GPX7 ) is a newly discovered non-selenium-containing protein with glutathione peroxidase activity, which mainly protects the organism from oxidative damage and is very important for basic biology studies. This study aims to reveal the expression pattern of GPX7 and its prognosis potential from a pan-cancer perspective. Methods Expression levels of GPX7 in human tumor tissues and normal tissues were evaluated using Human Protein Atlas (HPA), the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and UALCAN databases. The prognostic potential of GPX7 for 33 TCGA tumors was evaluated by Kaplan–Meier analysis and Cox regression analysis. Subsequently, the Chinese Glioma Genome Atlas (CGGA) dataset was used to further verify the expression of GPX7 and its prognostic potential in glioma. We explored the correlation between GPX7 and immune infiltration, tumor mutational burden (TMB) and microsatellite instability (MSI). Furthermore, a nomogram lower-grade glioma (LGG) was constructed to verify the prognostic outcome of patients. Finally, the relationship between GPX7 and treatment regimens for LGG was also explored. Results GPX7 was overexpressed in multiple tumors. Elevated expression of GPX7 was associated with poor prognosis of LGG patients (OS hazard ratio (HR) = 1.044, P < 0.0001; DFS HR = 1.035, P < 0.0001; PFS HR = 1.045, P < 0.0001). GPX7 was proved to be an independent prognostic factor of LGG through univariate and multivariate Cox analysis. The nomogram confirmed a better predictability (Concordance index (C-index): 0.845; 95% CI, 0.825–0.865). GPX7 was positively correlated with TMB in LGG. GPX7 expression was negatively correlated with half-maximal inhibitory concentration (IC50) of temozolomide (TMZ) ( spearman = −0.59, P =1.3e-48). Conclusion GPX7 was upregulated in multiple tumors, and it was a potential prognostic biomarker in LGG. High-expressed GPX7 can predict the sensitivity of TMZ in LGG patients.

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“…( 7 ) showed that GPX7 had an overexpression in hepatocellular carcinoma tissues. In glioma, only one bioinformatic study reported that GPX7 was a potential prognostic molecule based on Chinese Glioma Genome Atlas (CGGA) database ( 8 ). However, the mechanisms by which GPX7 might exert its actions in the development of glioma remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma

Zhou

Wang

et al. 2022

Front. Oncol.

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BackgroundGlioma is a lethal primary tumor of central nervous system. Ferroptosis is a newly identified form of necrotic cell death. Triggering ferroptosis has shown potential to eliminate aggressive tumors. GPX7, a member of glutathione peroxidase family (GPXs), has been described to participate in oxidative stress and tumorigenesis. However, the biological functions of GPX7 in glioma are still unknown.MethodsBioinformatics method was used to assess the prognostic role of GPX7 in glioma. CCK8, wound healing, transwell and cell apoptosis assays were performed to explore the functions of GPX7 in glioma cells. In vivo experiment was also conducted to confirm in vitro findings. Ferroptosis-related assays were carried out to investigate the association between GPX7 and ferroptosis in glioma.ResultsGPX7 was aberrantly expressed in glioma and higher expression of GPX7 was correlated with adverse outcomes. GPX7 silencing enhanced ferroptosis-related oxidative stress in glioma cells and the loss of GXP7 sensitized glioma to ferroptosis induced by erastin. Furthermore, we found that miR-29b directly suppressed GPX7 expression post-transcriptionally. Reconstitution of miR-29b enhanced erastin sensitivity, partly via GPX7 suppression.ConclusionsOur study clarified the prognostic role of GPX7 in glioma and preliminarily revealed the role of GPX7 in ferroptosis, which may be conducive to the exploration of therapeutic targets of glioma.

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The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients

Cited by 7 publications

References 22 publications

GPX7 is Identified as a Novel Prognostic Indicator for Brain Lower Grade Glioma (LGG): Evidence from a Pan-Cancer Analysis

GPX7 is Identified as a Novel Prognostic Indicator for Brain Lower Grade Glioma (LGG): Evidence from a Pan-Cancer Analysis

A Bioinformatic Analysis: The Overexpression and Prognostic Potential of GPX7 in Lower-Grade Glioma

GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma

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