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CD2-CD58 轴:预测低级别胶质瘤患者不良预后的新型标志物及潜在治疗途径

英文原题:The CD2-CD58 axis: A novel marker predicting poor prognosis in patients with low-grade gliomas and potential therapeutic approaches.

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The CD2-CD58 axis: A novel marker predicting poor prognosis in patients with low-grade gliomas and potential therapeutic approaches.

PubMed 2023/10/01(内容时间) Immun Inflamm Dis Q2 · IF 3.5(JCR 2025)

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研究概要

我们的研究结果强调了 CD2-CD58 轴与 LGG 患者不良生存率之间的显著关联。CD58 高表达作为一种免疫抑制因子参与 T 细胞介导的免疫反应,并影响抑制性免疫检查点基因。

研究思路结论见上方概要

低级别胶质瘤(LGGs)目前被认为是高级别胶质瘤(HGGs)的癌前病变,其特征是免疫系统相对完整。免疫治疗方式可能为这些患者提供一种安全有效的治疗选择。然而,作为免疫突触重要组成部分的CD2-CD58轴在LGG中仍属未知。

对来自 TCGA 数据库的 RNA-seq 数据进行了分析。采用基于已发表研究中整合免疫基因集的单样本基因集富集分析(ssGSEA)确定免疫细胞浸润。采用 Kaplan-Meier 生存分析、单因素和多因素 logistic 分析以及 ESTIMATE 算法评估 CD2-CD58 轴对成人 LGG 患者的影响。

CD2-CD58轴的表达随着WHO级别的升高而升高(p < .05)。单因素和多因素logistic分析表明,年龄、WHO级别和CD58水平与LGG患者的不良预后相关(p < .01)。MetaSape通路分析显示,CD58参与调控WHO II级和III级中的T细胞活化、白细胞介导的免疫以及细胞活化的正向调控。CD58表达与CD4+淋巴细胞、NK细胞和巨噬细胞的浸润相关。ESTIMATE算法表明,在WHO II/III级中,CD58高表达患者的免疫评分显著高于CD58低表达患者,但在WHO IV级中未观察到统计学差异(p < .05)。此外,相关性分析表明CD58与CD274(r = 0.581,p < .001)、HAVCR2(r = 0.58i7,p < .001)和LGALS9(r = 0.566,p < .001)之间存在显著关联。免疫组化染色进一步证实了CD58、HAVCR2、WHO级别与II级和III级患者预后之间的关系。

展开英文摘要原文

RNA-seq data from TCGA databases were analyzed. Immune cell infiltration was determined using a single-sample gene set enrichment analysis (ssGSEA) based on integrated immune gene sets from published studies. Kaplan-Meier survival analysis, univariate and multivariate logistic analysis, and the ESTIMATE algorithm were employed to evaluate the impact of the CD2-CD58 axis on adult LGG patients.

The expression of the CD2-CD58 axis was found to be elevated with increasing of WHO grade (p < .05). Uni- and multi-variable logistic analysis demonstrated that age, WHO grade, and CD58 levels were associated with poor prognosis in LGG patients with (p < .01). MetaSape pathways analysis revealed the involvement of CD58 in regulating T cell activation, leukocyte-mediated immunity, and the positive regulation of cell activation in WHO grade II and III. CD58 expression correlated with infiltrations of CD4+ lymphocytes, NK cells, and macrophages cells. The ESTIMATE algorithm indicated that patients with high CD58 expression had significantly higher immune scores compared with low CD58 expression in WHO grade II/III, but no statistical difference was observed in WHO grade IV (p < .05). Furthermore, correlation analysis demonstrated the significant association between CD58 and CD274 (r = 0.581, p < .001), HAVCR2 (r = 0.58i7, p < .001), and LGALS9 (r = 0.566, p < .001). Immunohistochemical staining further confirmed the relationship of CD58, HAVCR2, WHO grade, and prognosis in grade II and III patients.

Overall, our findings highlight the significant association between the CD2-CD58 axis and poor survival in LGG patients. High CD58 expression is implicated in T cell-mediated immune responses as an immunosuppressive factor and affect inhibitory immune checkpoint genes.

论文信息

作者
Wu M、Chen Y、Hua G、Chunhui L
第一作者单位
Qinzhou First People's Hospital, Qinzhou, China.China
通讯作者单位
Beijing Tiantan Hospital, Capital Medical University, Beijing, China.China
期刊
Immunity, inflammation and disease2023 Oct
原文标识
PubMed 37904707 · DOI 10.1002/iid3.1022