BMPR2 expression level is correlated with low immune infiltration and predicts metastasis and poor survival in osteosarcoma.
BMPR2 expression level is correlated with low immune infiltration and predicts metastasis and poor survival in osteosarcoma.
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DOI：
10.3892/ol.2021.12652
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发表时间：
2021-05
期刊：
影响因子：
2.9
通讯作者：
Jiao G
中科院分区：
文献类型：
--
作者：
Cao H;Quan S;Zhang L;Chen Y;Jiao G
骨肉瘤是青少年和青壮年中最常见的恶性骨肿瘤，确定预后和治疗的生物标志物是必要的。骨形态发生蛋白受体2 （BMPR2）参与多种细胞功能，包括细胞粘附、增殖和侵袭、炎症、凋亡和转移扩散。然而，BMPR2表达水平与骨肉瘤预后和肿瘤浸润免疫细胞之间的关系尚不清楚。在本研究中，使用Oncomine和R2数据库研究BMPR2的表达水平。采用R2数据库分析BMPR2表达水平与肿瘤患者临床预后的关系。采用肿瘤免疫估计资源（Tumor immune Estimation Resource， TIMER）和CIBERSORT评估骨肉瘤基质中BMPR2表达水平与免疫细胞浸润的关系。在TIMER和R2数据库中验证BMPR2表达水平与骨肉瘤浸润免疫细胞基因标记集的相关性。一项骨肉瘤患者队列分析显示，BMPR2在骨肉瘤中的表达明显高于正常组织，并与预后不良相关。M0巨噬细胞、M2巨噬细胞、静止肥大细胞、γ δ T细胞和CD8+ T细胞是骨肉瘤浸润程度最高的前5种免疫细胞。此外，BMPR2表达水平与CD8+ T细胞、单核细胞和M2巨噬细胞的基因标记物呈显著负相关。骨肉瘤中CD8+ T细胞、单核细胞或M2巨噬细胞浸润水平低与生存率低显著相关。这些数据提示CD8+ T细胞、单核细胞和M2巨噬细胞在骨肉瘤免疫微环境的建立中发挥重要作用。BMPR2高表达与骨肉瘤预后差、CD8+ T细胞、单核细胞和M2巨噬细胞浸润低相关。因此，BMPR2可以被认为是骨肉瘤免疫浸润、转移和预后的生物标志物。
Osteosarcoma is the most common malignant bone tumor in adolescents and young adults, and identifying biomarkers for prognosis and therapy is necessary. Bone morphogenetic protein receptor 2 (BMPR2) is involved in various cellular functions, including cell adhesion, proliferation and invasion, inflammation, apoptosis and metastatic spread. However, the correlation between BMPR2 expression levels and prognosis and tumor-infiltrating immune cells in osteosarcoma is not well understood. In the present study, the expression level of BMPR2 was investigated using the Oncomine and R2 databases. The association between the expression level of BMPR2 and the clinical prognosis of patients with cancer was analyzed using the R2 database. The relationship between the expression level of BMPR2 and immune cell infiltration in the stroma of osteosarcoma was assessed using the Tumor Immune Estimation Resource (TIMER) and CIBERSORT. The correlations between BMPR2 expression level and infiltrated immune cell gene marker sets in osteosarcoma were validated in the TIMER and R2 databases. Analysis of a cohort of patients with osteosarcoma revealed that BMPR2 expression was significantly higher in osteosarcoma compared with in normal tissue and was correlated with poor prognosis. M0 macrophages, M2 macrophages, resting mast, γ δ T and CD8+ T cells were the top five immune cells with the highest degrees of infiltration in osteosarcoma. In addition, BMPR2 expression level showed a significant negative correlation with the gene markers of CD8+ T cells, monocytes and M2 macrophages. Low levels of infiltrating CD8+ T cells, monocytes or M2 macrophages in osteosarcoma was significantly associated with poor survival. These data suggested that CD8+ T cells, monocytes and M2 macrophages play significant roles in the establishment of the immune microenvironment of osteosarcoma. High BMPR2 expression was associated with poor prognosis and low infiltration of CD8+ T cells, monocytes and M2 macrophages in osteosarcoma. Hence, BMPR2 can be considered a biomarker of the immune infiltration, metastasis and prognosis of osteosarcoma.
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影响因子：
11.5
作者：
Cutcliffe, C;Kersey, D;Perlman, EJ
通讯作者：
Perlman, EJ
影响因子：
7.3
作者：
Browning LM;Pietrzak M;Kuczma M;Simms CP;Kurczewska A;Refugia JM;Lowery DJ;Rempala G;Gutkin D;Ignatowicz L;Muranski P;Kraj P
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通讯作者：
Morrell NW
影响因子：
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作者：
Fritzsching, Benedikt;Fellenberg, Joerg;Kunz, Pierre
通讯作者：
Kunz, Pierre
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
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