Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.
Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, China.
Front Immunol. 2022 Aug 19;13:986785. doi: 10.3389/fimmu.2022.986785. eCollection 2022.
Recent studies have shown that tumor stemness has biological significance in tumorigenicity and tumor progression. However, the characteristics of TME immune infiltration in osteosarcoma mediated by the combined effects of multiple cancer stem cell-related genes remain unknown.
In this study, we identified different cancer stem cell-associated subtypes in osteosarcoma based on 25 cancer stem cell-associated genes by consensus clustering analysis, and we comprehensively evaluated the association between these subtypes and immunocytes infiltration in the TME. The cancer stem cell (CSC) score was constructed to quantify the stemness of individual tumors.
We performed a comprehensive evaluation of 218 osteosarcoma patients based on 25 cancer stem cell-related genes. Three different cancer stem cells related subtypes were identified, which were related to different biological processes and clinical outcomes. The three subtypes have different TME cells infiltrating characteristics, and CSC Cluster A had a higher level of immunocyte infiltration compared to CSC Cluster B and C. We constructed a scoring system, called the CSC score, to assess the stemness of individual patients. Then we found that the prognosis of patients was predicted by CSC score, and patients with low CSC score had prolonged survival. Further analyses showed that low CSC score was correlated with enhanced immune infiltration. CSC score may predict the effect of immunotherapy, and patients with low CSC score may have better immune response and clinical prognosis.
This study demonstrates that there could be three cancer stem cell-associated subtypes in osteosarcoma and that they were associated with different patient prognosis and TME immune infiltration characteristics. CSC score could be used to assess the stemness of individual patients, improve our comprehension of TME characteristics, and direct more effective immune therapy.
最近的研究表明，肿瘤干性在肿瘤发生和肿瘤进展中具有生物学意义。然而，由多个癌症干细胞相关基因的共同作用介导的骨肉瘤中肿瘤微环境免疫浸润的特征尚不清楚。
在这项研究中，我们通过共识聚类分析，基于 25 个癌症干细胞相关基因确定了骨肉瘤中不同的癌症干细胞相关亚型，并全面评估了这些亚型与肿瘤微环境中免疫细胞浸润的相关性。构建了癌症干细胞（CSC）评分来量化个体肿瘤的干性。
我们对 218 名骨肉瘤患者进行了基于 25 个癌症干细胞相关基因的综合评估。鉴定了三种不同的癌症干细胞相关亚型，它们与不同的生物学过程和临床结局相关。这三种亚型具有不同的 TME 细胞浸润特征，CSC 簇 A 比 CSC 簇 B 和 C 具有更高水平的免疫细胞浸润。我们构建了一个评分系统，称为 CSC 评分，用于评估个体患者的干性。然后我们发现 CSC 评分可以预测患者的预后，低 CSC 评分的患者生存时间延长。进一步的分析表明，低 CSC 评分与增强的免疫浸润相关。CSC 评分可能预测免疫治疗的效果，低 CSC 评分的患者可能具有更好的免疫反应和临床预后。
本研究表明，骨肉瘤中可能存在三种癌症干细胞相关亚型，它们与不同的患者预后和 TME 免疫浸润特征相关。CSC 评分可用于评估个体患者的干性，提高我们对 TME 特征的理解，并指导更有效的免疫治疗。
