背景:低级别神经胶质瘤(LGG)目前被认为是高级别神经胶质瘤(HGs)的癌前疾病,其特征在于相对完整的免疫系统。免疫治疗方式可以为这些患者提供安全有效的治疗选择。然而,CD2-CD58轴,免疫突触的重要组成部分,在LGG中仍然未知。
方法:分析来自TCGA数据库的RNA-seq数据。使用基于来自已发表研究的整合免疫基因集的单样品基因集富集分析(ssGSEA)来确定免疫细胞浸润。Kaplan-Meier生存分析,单变量和多变量逻辑分析,和ESTIMATE算法用于评估CD2-CD58轴对成年LGG患者的影响。
结果:发现CD2-CD58轴的表达随着WHO等级的增加而升高(p<.05)。单变量和多变量逻辑分析表明,年龄,WHO等级,和CD58水平与LGG患者的不良预后相关(p<0.01)。MetaSape通路分析显示CD58参与调节T细胞活化,白细胞介导的免疫,以及WHOII级和III级细胞活化的正向调节。CD58表达与CD4+淋巴细胞浸润相关,NK细胞,和巨噬细胞。ESTIMATE算法表明,在WHOII/III级中,与CD58低表达相比,CD58高表达的患者的免疫评分明显更高。但在WHOIV级中没有观察到统计学差异(p<.05)。此外,相关分析表明CD58和CD274之间存在显著关联(r=0.581,p<.001),HAVCR2(r=0.58i7,p<.001),和LGALS9(r=0.566,p<.001)。免疫组化染色进一步证实了CD58、HAVCR2、WHO分级、II级和III级患者的预后。
结论:总体而言,我们的研究结果强调了CD2-CD58轴与LGG患者生存不良之间的显著关联.高CD58表达作为免疫抑制因子参与T细胞介导的免疫应答并影响抑制性免疫检查点基因。
Low-grade gliomas (LGGs) are currently considered a premalignant condition for high-grade gliomas (HGGs) and are characterized by a relatively intact immune system. Immunotherapeutic modalities may offer a safe and effective treatment option for these patients. However, the CD2-CD58 axis, an important component of the immunological synapse, remains unknown in LGG.
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.