Comprehensive landscape of STEAP family functions and prognostic prediction value in glioblastoma

Background Gliomas are primary aggressive brain tumors with poor prognoses. Oxidative stress plays a crucial role in the tumorigenesis and drug resistance of gliomas. The aim of the present study was to use integrated bioinformatics analyses to evaluate the prognostic value of oxidative stress-related genes (OSRGs) in glioma. Material/Methods Disease- and prognosis-associated OSRGs were identified using microarray and clinical data from the Chinese Glioma Genome Atlas database. Functional enrichment, gene-gene interaction, protein-protein interaction, and survival analyses were performed in screened OSRGs. The protein expression was validated by the Human Protein Atlas database. A risk score model was constructed and verified through Cox regression, receiver operating characteristic curve, principal component, and stratified analyses. The Cancer Genome Atlas (TCGA) database was used for external validation. A nomogram was constructed to facilitate the clinical application. Results Twenty-one disease-associated and 14 prognosis-associated OSRGs were identified. Enrichment analyses indicated that these signature OSRGs were involved in tumorigenesis and drug resistance of glioma. The risk score model demonstrated a significant difference in overall survival between the high- and low-risk groups. The area under the curve and hazard ratio (1.296) revealed the independent prognostic value of the model. The model exhibited good predictive efficacy in the TCGA cohort. A clinical nomogram was constructed to calculate survival rates in glioma patients at 1, 3, and 5 years. Conclusions Our comprehensive study indicated that OSRGs were valuable for prognosis prediction in glioma, which provides a novel insight into the relationship between oxidative stress and glioma and a potential therapeutic strategy for glioma patients.

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“…No significant differences were detected in radiotherapy status. Similar results were also reported by Chen et al [ 30 ].…”

Section: Resultssupporting

confidence: 92%

Identifying the Predictive Role of Oxidative Stress Genes in the Prognosis of Glioma Patients

Wang

Liu

et al. 2021

Med Sci Monit

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“…STEAP members have been identified as important metalloreductases in vivo and been shown to play a role in iron homeostasis [ 48 ]. They have also been shown to have precise performance in predicting the outcomes of glioma patients [ 49 ]. However, the STEAP family focused on survival time rather than response to immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma

Luo

Wang

Liao³

et al. 2021

IJMS

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Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) has been identified as a group of enzymes that catalyze cytosine deamination in single-stranded (ss) DNA to form uracil, causing somatic mutations in some cancers. We analyzed the APOBEC3 family in 33 TCGA cancer types and the results indicated that APOBEC3s are upregulated in multiple cancers and strongly correlate with prognosis, particularly in low grade glioma (LGG). Then we constructed a prognostic model based on family expression in LGG where the APOBEC3 family signature is an accurate predictive model (AUC of 0.85). Gene mutation, copy number variation (CNV), and a differential gene expression (DEG) analysis were performed in different risk groups, and the weighted gene co-expression network analysis (WGCNA) was employed to clarify the role of various members in LGG; CIBERSORT algorithm was deployed to evaluate the landscape of LGG immune infiltration. We found that upregulation of the APOBEC3 family expression can strengthen Ras/MAPK signaling pathway, promote tumor progression, and ultimately reduce the treatment benefits of Raf inhibitors. Moreover, the APOBEC3 family was shown to enhance the immune response mediated by myeloid cells and interferon gamma, as well as PD-L1 and PD-L2 expression, implying that they have immunotherapy potential. Therefore, the APOBEC3 signature enables an efficient assessment of LGG patient survival outcomes and expansion of clinical benefits by selecting appropriate individualized treatment strategies.

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“…The expression STEAPs also exhibits an upregulation in tumors and they can promote tumor cell proliferation as well as suppress apoptosis (70)(71)(72)(73), for example, STEAP3 promotes glioma cell proliferation, invasion, and spheroid formation by inducing mesenchymal transformation, promoting TFR1 expression, and activating the STAT3-FoxM1 axis (39); In colorectal cancer, STEAP3 expression is significantly higher in tumor than that in colonic mucosa (74). However, they recently found that silencing lncRNA STEAP3-AS1(the antisense transcript of STEAP3) inhibited the proliferation, migration, and arrested colon cancer cells at the G0-G1 phase cancer cells through upregulation STEAP3 (75).…”

Section: Steapsmentioning

confidence: 99%

The Role of Iron in Cancer Progression

et al. 2021

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Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. In addition, iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. Here, we reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors.

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Comprehensive landscape of STEAP family functions and prognostic prediction value in glioblastoma

Cited by 48 publications

References 35 publications

Identifying the Predictive Role of Oxidative Stress Genes in the Prognosis of Glioma Patients

Identifying the Predictive Role of Oxidative Stress Genes in the Prognosis of Glioma Patients

Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma

The Role of Iron in Cancer Progression

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