Macrophages infiltration in low grade glioma and its value in prognosis prediction

Abstract

Objective To detect the infiltration degree and functional state of tumor-associated macrophages (TAM) in different low-grade glioma (LGG) subtypes, and to analyze the value of TAM related biomarkers in predicting patient prognosis. Methods We downloaded 529 cases LGG data from The Cancer Genome Atlas (TCGA), and compared the expression levels of TAM infiltration biomarkers between IDH 1/2-wt LGG and IDH 1/2-mu LGG. CD163 and IL- 10 were used to predict patient prognosis. We also detected the infiltration degree of TAM by immunohistochemistry in 17 IDH 1/2-wt and 19 IDH 1/2-mu LGG clinical samples. Mann-Whitney U test, COX regression and Kaplan-Meier method were used for statistical analysis. Results TCGA data analysis showed that the expression levels of macrophages and TAM markers CD68 (Mann- Whitney U = 19425, P = 0.01), CD11b (Mann-Whitney U = 15836, P < 0.01), IBA1 (Mann- Whitney U = 17758, P < 0.01),CD163 (Mann-Whitney U = 18112, P < 0.01),CD204 (Mann- Whitney U = 12676, P < 0.01) in IDH 1/2-wt LGG were significantly higher than IDH 1/2 -mu LGG. Meanwhile, the infiltration degree of TAM in clinical glioma tissues was higher in IDH 1/2- wt LGG compared to IDH 1/2-mu LGG (Mann-Whitney U = 51, P < 0.01; Mann-Whitney U = 35, P < 0.01; Mann- Whitney U = 20, P < 0.01). IDH 1/2-wt LGG expressed more TAM chemokines CCL2 (Mann- Whitney U = 15841, P < 0.01), CCL5 (Mann-Whitney U = 11 326, P < 0.01), POSTN (Mann- Whitney U = 8 893, P < 0.01), VEGF-A (Mann-Whitney U = 14433, P < 0.01), Neurotensin (Mann-Whitney U = 15 556, P < 0.01) than IDH 1/2-mu LGG. Additionally, the expression levels of TGF-β (Mann-Whitney U = 15 459, P < 0.01)和IL-10 (Mann-Whitney U = 17 334, P < 0.01) produced by TAM were significantly up- regulated in IDH 1/2-wt LGG. Furthermore, survival analysis showed that in the IDH 1/2-wt group, the overall survival rate of the CD163high patients was lower than the CD163low patients (P = 0.01), and the overall survival rate of the IL-10high patients was lower than IL-10low patients in the IDH 1/2-mu LGG patients (P < 0.05). Conclusion The infiltration numbers of TAM and immunosuppression states are different between IDH 1/2-wt LGG and IDH 1/2 -mu LGG. The expression level of CD163 is negatively correlated with prognosis of IDH 1/2-wt LGG patients, and the expression level of IL-10 is negatively correlated with prognosis of IDH 1/2-mu LGG patients Key words: Glioma; Tumor-associated macrophages; Isocitrate dehydrogenase