Li Shihao, Yuan Qiong, Zhang Yuanyuan, Zhang Haiyang
Department of Orthopedics, Zibo Central Hospital, West Campus, Zhangdian District, Zibo, Shandong Province, 255036, P.R. China.
Department of Anesthesiology and Surgery, Zibo Central Hospital, Zhangdian District, Zibo, Shandong Province, 255036, P.R. China.
BMC Musculoskelet Disord. 2025 Mar 31;26(1):309. doi: 10.1186/s12891-024-08231-1.
Neutrophil extracellular trap (NET) has been implicated in cancer progression and metastasis. Nevertheless, the role of the NET-related gene, formyl peptide receptor 1 (FPR1), in osteosarcoma (OS) remains largely unexplored. This study aimed to investigate the prognostic significance and biological function of FPR1 in OS.
The least absolute shrinkage and selection operator (LASSO) algorithm was employed to construct a NET-related prognostic model utilizing OS datasets from TARGET and GEO (GSE21257) databases. The scRNA-seq dataset GSE162454 was then used for verifying the role of NET-related model in OS at single-cell resolution. Next, survival analysis and multivariate cox regression analysis were performed to evaluate the prognostic value of FPR1 in OS patients. The CIBERSORT algorithm was conducted to evaluate the relationship between FPR1 levels and immune cell abundance. Subsequently, the biological role of FPR1 was explored through CCK-8, and transwell assays in OS cell lines.
A signature NET score, comprising four NET-related genes (TNFRSF10C, FPR1, BST1 and SELPLG), was constructed to predict the prognosis of OS. The survival outcomes for patients in high-NET score group were markedly worse than that in the low-NET score group. Meanwhile, at single cell resolution, OS cells progressively evolved into tumors with elevated NET scores. Furthermore, FPR1 levels were markedly reduced in OS cells when compared to normal osteoblast cells, and the overexpression of FPR1 notably suppressed OS cell viability, migration and invasion. Additionally, OS patients exhibiting high levels of FPR1 demonstrated a favorable overall survival. Moreover, these patients also had a higher proportion of M1 macrophages and a lower proportion of M0 macrophages.
Collectively, our study indicates that the NET-related gene FPR1 is closely related to tumor progression, prognosis and immune infiltration in OS.
中性粒细胞胞外陷阱（NET）与癌症进展和转移有关。然而，NET相关基因甲酰肽受体1（FPR1）在骨肉瘤（OS）中的作用在很大程度上仍未得到探索。本研究旨在探讨FPR1在OS中的预后意义和生物学功能。
采用最小绝对收缩和选择算子（LASSO）算法，利用来自TARGET和GEO（GSE21257）数据库的OS数据集构建一个NET相关的预后模型。然后使用单细胞RNA测序（scRNA-seq）数据集GSE162454在单细胞分辨率下验证NET相关模型在OS中的作用。接下来，进行生存分析和多变量cox回归分析，以评估FPR1在OS患者中的预后价值。使用CIBERSORT算法评估FPR1水平与免疫细胞丰度之间的关系。随后，通过CCK-8和OS细胞系中的transwell实验探索FPR1的生物学作用。
构建了一个由四个NET相关基因（TNFRSF10C、FPR1、BST1和SELPLG）组成的特征性NET评分，以预测OS的预后。高NET评分组患者的生存结果明显比低NET评分组差。同时，在单细胞分辨率下，OS细胞逐渐演变成NET评分升高的肿瘤。此外，与正常成骨细胞相比，OS细胞中FPR1水平明显降低，FPR1的过表达显著抑制了OS细胞的活力、迁移和侵袭。此外，FPR1水平高的OS患者总体生存率良好。而且，这些患者中M1巨噬细胞的比例较高，M0巨噬细胞的比例较低。
总体而言，我们的研究表明，NET相关基因FPR1与OS中的肿瘤进展、预后和免疫浸润密切相关。
