IFI30 expression is an independent unfavourable prognostic factor in glioma.

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Journal of Cellular and Molecular Medicine Pub Date : 2020-11-01 Epub Date: 2020-09-23 DOI:10.1111/jcmm.15758
Xiu Liu, Chunyan Song, Shoubo Yang, Qiang Ji, Feng Chen, Wenbin Li
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引用次数: 13

Abstract

Gamma-interferon-inducible lysosomal thiol reductase, the only known lysosomal thiol reductase, is encoded by gene IFI30 and expressed constitutively in antigen-presenting cells. Our comprehensive study on IFI30 in gliomas found its expression to be high in glioblastomas and in gliomas with a mesenchymal subtype or wild-type isocitrate dehydrogenase, all of which indicated the malignancy and poor outcomes of gliomas. Kaplan-Meier survival analysis ascertained that high IFI30 expression conferred poor outcomes. The IFI30 expression levels also showed high efficiency in predicting 1-, 3- and 5-year overall survival. Univariable and multivariable Cox regression analyses were performed to define IFI30 as an independent prognostic marker. Biological process analysis suggested that IFI30 was involved in immune responses. ESTIMATE and CIBERSORT were applied to evaluate immune cell infiltration, with results indicating that samples with higher IFI30 expression had higher infiltration of immune cells, including regulatory T cells and M0 macrophages. Correlation analysis showed that IFI30 was significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses. Immunohistochemical staining was also performed to confirm the association between IFI30 expression and the immune phenotype. The suggested correlation between high IFI30 expression and an immunosuppressive phenotype contributes to our knowledge about the glioma microenvironment and might provide clues for the development of novel therapeutic targets.

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IFI30的表达是胶质瘤中一个独立的不利预后因素。
γ干扰素诱导型溶酶体硫醇还原酶是目前已知的唯一一种溶酶体硫醇还原酶,由基因IFI30编码,在抗原提呈细胞中组成性表达。我们在胶质瘤中的综合研究发现,IFI30在胶质瘤母细胞瘤和间充质亚型或野生型异柠檬酸脱氢酶的胶质瘤中高表达,提示胶质瘤的恶性和预后不良。Kaplan-Meier生存分析确定IFI30高表达导致预后差。IFI30表达水平在预测1年、3年和5年总生存率方面也显示出高效率。通过单变量和多变量Cox回归分析,将IFI30定义为独立的预后指标。生物学过程分析表明IFI30参与免疫应答。应用ESTIMATE和CIBERSORT评估免疫细胞浸润,结果显示IFI30表达高的样品免疫细胞浸润量高,包括调节性T细胞和M0巨噬细胞。相关分析显示IFI30与抑制有效抗肿瘤免疫应答的免疫检查点显著正相关。免疫组织化学染色也证实了IFI30表达与免疫表型之间的关联。IFI30高表达与免疫抑制表型之间的相关性有助于我们了解胶质瘤微环境,并可能为开发新的治疗靶点提供线索。
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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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