Identification and validation of SOCS1/2/3/4 as potential prognostic biomarkers and correlate with immune infiltration in glioblastoma

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Journal of Cellular and Molecular Medicine Pub Date : 2023-06-14 DOI:10.1111/jcmm.17807
Lirui Dai, Yongjie Han, Zhuo Yang, Yuling Zeng, Wulong Liang, Zimin Shi, Yiran Tao, Xianyin Liang, Wanqing Liu, Shaolong Zhou, Zhe Xing, Weihua Hu, Xinjun Wang
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Abstract

Suppressor of cytokine signalling (SOCS) 1/2/3/4 are involved in the occurrence and progression of multiple malignancies; however, their prognostic and developmental value in patients with glioblastoma (GBM) remains unclear. The present study used TCGA, ONCOMINE, SangerBox3.0, UALCAN, TIMER2.0, GENEMANIA, TISDB, The Human Protein Atlas (HPA) and other databases to analyse the expression profile, clinical value and prognosis of SOCS1/2/3/4 in GBM, and to explore the potential development mechanism of action of SOCS1/2/3/4 in GBM. The majority of analyses showed that SOCS1/2/3/4 transcription and translation levels in GBM tissues were significantly higher than those in normal tissues. qRT-PCR, western blotting (WB) and immunohistochemical staining were used to verify that SOCS3 was expressed at higher mRNA and protein levels in GBM than in normal tissues or cells. High SOCS1/2/3/4 mRNA expression was associated with poor prognosis in patients with GBM, especially SOCS3. SOCS1/2/3/4 were highly contraindicated, which had few mutations, and were not associated with clinical prognosis. Furthermore, SOCS1/2/3/4 were associated with the infiltration of specific immune cell types. In addition, SOCS3 may affect the prognosis of patients with GBM through JAK/STAT signalling pathway. Analysis of the GBM-specific protein interaction (PPI) network showed that SOCS1/2/3/4 were involved in multiple potential carcinogenic mechanisms of GBM. In addition, colony formation, Transwell, wound healing and western blotting assays revealed that inhibition of SOCS3 decreased the proliferation, migration and invasion of GBM cells. In conclusion, the present study elucidated the expression profile and prognostic value of SOCS1/2/3/4 in GBM, which may provide potential prognostic biomarkers and therapeutic targets for GBM, especially SOCS3.

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鉴定和验证SOCS1/2/3/4作为潜在的预后生物标志物,并与胶质母细胞瘤免疫浸润相关
细胞因子信号传导抑制因子(SOCS) 1/2/3/4参与多种恶性肿瘤的发生和发展;然而,它们在胶质母细胞瘤(GBM)患者中的预后和发育价值尚不清楚。本研究利用TCGA、ONCOMINE、SangerBox3.0、UALCAN、TIMER2.0、GENEMANIA、TISDB、The Human Protein Atlas (HPA)等数据库,分析SOCS1/2/3/4在GBM中的表达谱、临床价值及预后,探讨SOCS1/2/3/4在GBM中的潜在发展机制。大多数分析显示,SOCS1/2/3/4在GBM组织中的转录和翻译水平显著高于正常组织。采用qRT-PCR、western blotting (WB)和免疫组化染色证实,SOCS3在GBM中的mRNA和蛋白表达水平高于正常组织或细胞。SOCS1/2/3/4 mRNA高表达与GBM患者预后不良相关,尤其是SOCS3。SOCS1/2/3/4为高度禁忌症,突变较少,与临床预后无关。此外,SOCS1/2/3/4与特定免疫细胞类型的浸润有关。此外,SOCS3可能通过JAK/STAT信号通路影响GBM患者的预后。对GBM特异性蛋白相互作用(PPI)网络的分析表明,socs1 / 2/2/3 /4参与了GBM的多种潜在致癌机制。此外,菌落形成、Transwell、创面愈合和western blotting实验显示,SOCS3的抑制抑制了GBM细胞的增殖、迁移和侵袭。综上所述,本研究阐明了SOCS1/2/3/4在GBM中的表达谱及其预后价值,可能为GBM尤其是SOCS3的预后提供潜在的生物标志物和治疗靶点。
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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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Immunosuppressive SOX9-AS1 Resists Triple-Negative Breast Cancer Senescence Via Regulating Wnt Signalling Pathway. Nodularin-R Synergistically Enhances Abiraterone Against Castrate- Resistant Prostate Cancer via PPP1CA Inhibition. Issue Information Issue Information Transcriptome analysis of six tissues obtained post-mortem from sepsis patients
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