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STEAP3是胶质母细胞瘤潜在的初步预后生物标志物。

STEAP3 is a potential preliminary prognostic biomarker of glioblastoma.

作者信息

Zhang Wenhua, Xie Meng, Huang Qiang, Liu Honglei, Liu Jianfeng, Sun Xiaoli, Li Conghui

机构信息

Department of Neurosurgery, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.

Department of Pediatrics, Shijiazhuang People,s Hospital, Shijiazhuang, 050000, Hebei, China.

出版信息

Sci Rep. 2024 Dec 28;14(1):30994. doi: 10.1038/s41598-024-82145-9.

DOI:10.1038/s41598-024-82145-9
PMID:39730631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11681130/
Abstract

Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a member of the iron regulation protein family, is characterized by a high recurrence rate and a short survival time. Nevertheless, studies investigating the role of STEAP3 in glioblastoma (GB) are scarce. In this study, the prognostic value of STEAP3 was evaluated utilizing mRNA expression profiles from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases as the validation and training cohorts, respectively. Moreover, differentially expressed genes were subjected to a functional enrichment analysis. The relationship between STEAP3 and the tumor microenvironment (TME) was examined. The immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) score were used to investigate response to immunotherapy. In all cohorts, GB patients with higher STEAP3 expression levels exhibited shorter overall survival (OS). Additionally, STEAP3-associated genes were primarily implicated in leukocyte migration, the JAK-STAT signaling pathway, and the cytokine-mediated signaling pathway. In the STEAP3 high-expression group, the ESTIMATEScore, ImmuneScore, StromalScore, and IPS were significantly higher. Overall, our results highlighted that STEAP3 might serve as a candidate prognostic biomarker for GB. Additionally, it might regulate the TME and influence GB metastasis.

摘要

前列腺六跨膜上皮抗原3(STEAP3)是铁调节蛋白家族的一员,其特点是复发率高、生存时间短。然而,关于STEAP3在胶质母细胞瘤(GB)中作用的研究很少。在本研究中,分别利用基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库中的mRNA表达谱作为验证队列和训练队列,评估STEAP3的预后价值。此外,对差异表达基因进行了功能富集分析。研究了STEAP3与肿瘤微环境(TME)之间的关系。使用免疫表型评分(IPS)和肿瘤免疫功能障碍与排除(TIDE)评分来研究对免疫治疗的反应。在所有队列中,STEAP3表达水平较高的GB患者总生存期(OS)较短。此外,与STEAP3相关的基因主要涉及白细胞迁移、JAK-STAT信号通路和细胞因子介导的信号通路。在STEAP3高表达组中,ESTIMATEScore、免疫评分、基质评分和IPS显著更高。总体而言,我们的结果表明,STEAP3可能作为GB的候选预后生物标志物。此外,它可能调节TME并影响GB转移。

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本文引用的文献

1
Potential diagnostic and drug target markers in glioblastoma.胶质母细胞瘤的潜在诊断和药物靶点标志物。
Sci Rep. 2024 Mar 27;14(1):7292. doi: 10.1038/s41598-024-57752-1.
2
STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway.STEAP3 通过调节 p53/SLC7A11 通路影响卵巢癌进展,导致铁死亡。
Mediators Inflamm. 2024 Feb 26;2024:4048527. doi: 10.1155/2024/4048527. eCollection 2024.
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Research of STEAP3 interaction with Rab7A and RACK1 to modulate the MAPK and JAK/STAT signaling in Osteoarthritis.
STEAP3 与 Rab7A 和 RACK1 的相互作用研究调节骨关节炎中的 MAPK 和 JAK/STAT 信号通路。
Int Immunopharmacol. 2023 Nov;124(Pt B):111034. doi: 10.1016/j.intimp.2023.111034. Epub 2023 Oct 9.
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Identification of INSRR as an immune-related gene in the tumor microenvironment of glioblastoma by integrated bioinformatics analysis.通过综合生物信息学分析鉴定胰岛素受体相关受体(INSRR)为胶质母细胞瘤肿瘤微环境中的免疫相关基因。
Med Oncol. 2023 Apr 26;40(6):161. doi: 10.1007/s12032-023-02023-8.
5
JAK-STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States.JAK-STAT 信号通路在炎症性乳腺癌中可使化疗耐药细胞状态。
Cancer Res. 2023 Jan 18;83(2):264-284. doi: 10.1158/0008-5472.CAN-22-0423.
6
KEGG for taxonomy-based analysis of pathways and genomes.KEGG 用于基于分类的途径和基因组分析。
Nucleic Acids Res. 2023 Jan 6;51(D1):D587-D592. doi: 10.1093/nar/gkac963.
7
Targeting ferroptosis as a vulnerability in cancer.针对癌症中的铁死亡脆弱性。
Nat Rev Cancer. 2022 Jul;22(7):381-396. doi: 10.1038/s41568-022-00459-0. Epub 2022 Mar 25.
8
IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma.IFNγ 通过增加 JAK-STAT 通路的激活来增强铁死亡,从而抑制肾上腺皮质癌中 SLCA711 的表达。
Oncol Rep. 2022 May;47(5). doi: 10.3892/or.2022.8308. Epub 2022 Mar 24.
9
Significance of CD47 and Its Association With Tumor Immune Microenvironment Heterogeneity in Ovarian Cancer.CD47 表达的意义及其与卵巢癌肿瘤免疫微环境异质性的关系。
Front Immunol. 2021 Dec 13;12:768115. doi: 10.3389/fimmu.2021.768115. eCollection 2021.
10
STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma.STEAP3 通过促进 EGFR 的核易位促进肝癌细胞增殖,从而增强 RAC1-ERK-STAT3 信号通路。
Cell Death Dis. 2021 Nov 5;12(11):1052. doi: 10.1038/s41419-021-04329-9.