Shen Zhi-Long, Chen Zhao-Yu, Ji Yong, Jiang Hao, Zhu Zhi-Peng, Yuan Hao, Li Bo, Xu Wei, Xiao Jianru
Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
The Department of Spine Surgery II, Strategic Support Force Medical Center, Beijing, China.
J Oncol. 2023 Feb 17;2023:3677789. doi: 10.1155/2023/3677789. eCollection 2023.
The tumor microenvironment (TME) acts as a crucial role in the occurrence and development of osteosarcoma (OS). Despite this, the mechanism controlling the components of immunity and stroma in the tumor microenvironment remains a mystery. To conduct this study, we download and collate transcriptome data from the TARGET database, whose full name is Therapeutically Applicable Research to Generate Effective Treatments, as well as available clinical information of OS. The CIBERSORT and ESTIMATE methodology are used to acquire the proportions of components of immunity and stroma and tumor-infiltrating immune cells (TICs). Protein-protein interaction (PPI) networks and Cox regression analysis are used to select differentially expressed genes (DEGs). A prognostic biomarker is determined by intersecting univariate COX and PPI results, which lead to the finding of Triggering receptor expressed on myeloid cells-2 (TREM2). Based on the next analysis, TREM2 expression is positively correlated with OS survival time. Immune function-related genes have enrichment in the group with high expression of TREM2, according to gene set enrichment analysis (GSEA). The percentage of TICs by CIBERSORT methodology revealed that the expression of TREM2 is positively associated with follicular helper T cells, CD8-positive T cells, and M2 macrophages and negatively correlated with plasma cells, M0 macrophages, and naive CD4-positive T cells. All results suggest a possible integral role of TREM2 in the immune-related events of TME. Therefore, TREM2 may be a potential indicator of remodeling of TME in osteosarcoma, which is useful and helpful in predicting the clinical prognostic outcome of OS patients and provide a unique perspective for immunotherapy for OS.
肿瘤微环境(TME)在骨肉瘤(OS)的发生和发展中起着关键作用。尽管如此,控制肿瘤微环境中免疫和基质成分的机制仍然是个谜。为了开展这项研究,我们从TARGET数据库(全称为“生成有效治疗方法的治疗应用研究”)下载并整理了转录组数据以及OS的可用临床信息。使用CIBERSORT和ESTIMATE方法来获取免疫和基质成分以及肿瘤浸润免疫细胞(TICs)的比例。通过蛋白质-蛋白质相互作用(PPI)网络和Cox回归分析来选择差异表达基因(DEGs)。通过将单变量COX和PPI结果相交来确定一个预后生物标志物,这导致发现了髓系细胞上表达的触发受体2(TREM2)。基于后续分析,TREM2表达与OS生存时间呈正相关。根据基因集富集分析(GSEA),免疫功能相关基因在TREM2高表达组中富集。通过CIBERSORT方法得到的TICs百分比显示,TREM2的表达与滤泡辅助性T细胞、CD8阳性T细胞和M2巨噬细胞呈正相关,与浆细胞、M0巨噬细胞和幼稚CD4阳性T细胞呈负相关。所有结果表明TREM2在TME的免疫相关事件中可能发挥整体作用。因此,TREM2可能是骨肉瘤中TME重塑的潜在指标,这对于预测OS患者的临床预后结果是有用且有帮助的,并为OS的免疫治疗提供了独特的视角。