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

Abstract

IntroductionLow‐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.MethodsRNA‐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.ResultsThe 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.ConclusionOverall, 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.

Clinical significance of immune-related antigen CD58 in gliomas and analysis of its potential core related gene clusters

“…Data from The Encyclopedia of DNA Elements (ENCODE) suggest that CD58 may function as one of the NF-κB binding sites involved in glioma progression [ 26 ]. Wu et al also found that the CD2 − CD58 axis is involved in the progression of low-grade gliomas with the cancer genome atlas program (TCGA) database [ 27 ]. However, large-scale population analysis on the correlation between CD58 and the prognosis of glioma, as well as reports on the gene clusters involved in CD58 function in gliomas, are currently lacking.…”