Cao Hongxin, Quan Shuang, Zhang Lu, Chen Yunzhen, Jiao Guangjun
Department of Medical Oncology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Key Laboratory of Chemical Biology, Ministry of Education, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Lett. 2021 May;21(5):391. doi: 10.3892/ol.2021.12652. Epub 2021 Mar 18.
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.
骨肉瘤是青少年和年轻成年人中最常见的恶性骨肿瘤，因此有必要识别用于预后和治疗的生物标志物。骨形态发生蛋白受体2（BMPR2）参与多种细胞功能，包括细胞黏附、增殖和侵袭、炎症、凋亡以及转移扩散。然而，骨肉瘤中BMPR2表达水平与预后及肿瘤浸润免疫细胞之间的相关性尚未得到充分了解。在本研究中，利用Oncomine和R2数据库调查了BMPR2的表达水平。使用R2数据库分析了BMPR2表达水平与癌症患者临床预后之间的关联。利用肿瘤免疫估计资源（TIMER）和CIBERSORT评估了BMPR2表达水平与骨肉瘤基质中免疫细胞浸润的关系。在TIMER和R2数据库中验证了骨肉瘤中BMPR2表达水平与浸润免疫细胞基因标志物集之间的相关性。对一组骨肉瘤患者的分析显示，与正常组织相比，骨肉瘤中BMPR2表达显著更高，且与预后不良相关。M0巨噬细胞、M2巨噬细胞、静息肥大细胞、γδT细胞和CD8+T细胞是骨肉瘤中浸润程度最高的前五种免疫细胞。此外，BMPR2表达水平与CD8+T细胞、单核细胞和M2巨噬细胞的基因标志物呈显著负相关。骨肉瘤中浸润的CD8+T细胞、单核细胞或M2巨噬细胞水平低与生存不良显著相关。这些数据表明，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不良以及CD8+T细胞、单核细胞和M2巨噬细胞浸润低相关。因此，BMPR2可被视为骨肉瘤免疫浸润、转移和预后的生物标志物。
