Graduate School, Guangxi University of Chinese Medicine, Nanning 530001, China.
Department of Cardiology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, China.
Aging (Albany NY). 2020 Feb 9;12(4):3486-3501. doi: 10.18632/aging.102824.
This work aimed to investigate tumor-infiltrating immune cells (TIICs) and immune-associated genes in the tumor microenvironment of osteosarcoma. An algorithm known as ESTIMATE was applied for immune score assessment, and osteosarcoma cases were assigned to the high and low immune score groups. Immune-associated genes between these groups were compared, and an optimal immune-related risk model was built by Cox regression analyses. The deconvolution algorithm (referred to as CIBERSORT) was applied to assess 22 TIICs for their amounts in the osteosarcoma microenvironment. Osteosarcoma cases with high immune score had significantly improved outcome (P<0.01). The proportions of naive B cells and M0 macrophages were significantly lower in high immune score tissues compared with the low immune score group (P<0.05), while the amounts of M1 macrophages, M2 macrophages, and resting dendritic cells were significantly higher (P<0.05). Important immune-associated genes were determined to generate a prognostic model by Cox regression analysis. Interestingly, cases with high risk score had poor outcome (P<0.01). The areas under the curve (AUC) for the risk model in predicting 1, 3 and 5-year survival were 0.634, 0.781, and 0.809, respectively. Gene set enrichment analysis suggested immunosuppression in high-risk osteosarcoma patients, in association with poor outcome.
本研究旨在探讨骨肉瘤肿瘤微环境中的肿瘤浸润免疫细胞(TIICs)和免疫相关基因。采用 ESTIMATE 算法评估免疫评分,并将骨肉瘤病例分为高免疫评分组和低免疫评分组。比较两组间的免疫相关基因,并通过 Cox 回归分析构建最佳免疫相关风险模型。应用去卷积算法(CIBERSORT)评估 22 种 TIIC 在骨肉瘤微环境中的含量。高免疫评分组骨肉瘤病例的预后明显改善(P<0.01)。与低免疫评分组相比,高免疫评分组织中幼稚 B 细胞和 M0 巨噬细胞的比例显著降低(P<0.05),而 M1 巨噬细胞、M2 巨噬细胞和静息树突状细胞的含量显著升高(P<0.05)。通过 Cox 回归分析确定重要的免疫相关基因,构建预后模型。有趣的是,高风险评分病例的预后较差(P<0.01)。该风险模型预测 1、3 和 5 年生存率的曲线下面积(AUC)分别为 0.634、0.781 和 0.809。基因集富集分析表明,高风险骨肉瘤患者存在免疫抑制,与不良预后相关。