Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong University, 76 Nanguo Road, Xi'an, China.
The Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, China.
Gene. 2024 Nov 15;927:148645. doi: 10.1016/j.gene.2024.148645. Epub 2024 Jun 5.
Osteosarcoma is a common malignant tumor with a low survival rate after metastasis. Current treatments have not proven to effectively increase patient survival rates. Immunotherapy is a promising new treatment approach, however, immune target therapy has not shown satisfactory results. This study aims to provide new insights and evidence for the use of immunotherapy in osteosarcoma, based on a comprehensive analysis of gene expression data from databases.
Gene expression and GSAV analysis were conducted on samples from patients with metastatic and non-metastatic osteosarcoma in the TARGET and GEO databases to identify relevant genes. These genes were further analyzed using GO, KEGG, GSVA, correlation analysis, and immune microenvironment scoring techniques. The tissue location of gene expression was confirmed through single-cell analysis. Validation of gene expression patterns was performed using polymerase chain reaction, western blot, and immunohistochemistry.
The study identified FUCA1 and NCKAP1L as significantly enriched in non-metastatic osteosarcoma, with higher expression associated with better patient survival rates. Gene function enrichment was primarily related to immune functions, with positive correlations to macrophage phagocytosis, antigen presentation, and macrophage polarization pathways. Analysis of the immune microenvironment revealed a positive correlation between gene expression and immune scores, with increased presence of macrophages, T cells, and B cells in the high expression group. Single-cell analysis and experimental results confirmed the enrichment of FUCA1 and NCKAP1L in macrophages.
The identification of FUCA1 and NCKAP1L as potential prognostic biomarkers suggests their potential for improving patient outcomes. Modulation of macrophages may offer a promising strategy for enhancing the immune microenvironment in osteosarcoma.
骨肉瘤是一种常见的恶性肿瘤，转移后生存率较低。目前的治疗方法并未证明能有效提高患者的生存率。免疫疗法是一种很有前途的新治疗方法，然而免疫靶向治疗的效果并不理想。本研究旨在通过对数据库中的基因表达数据进行综合分析，为骨肉瘤的免疫治疗提供新的见解和依据。
在 TARGET 和 GEO 数据库中对转移性和非转移性骨肉瘤患者的样本进行基因表达和 GSAV 分析，以鉴定相关基因。进一步采用 GO、KEGG、GSVA、相关性分析和免疫微环境评分技术对这些基因进行分析。通过单细胞分析确认基因表达的组织位置。采用聚合酶链反应、western blot 和免疫组化验证基因表达模式。
研究发现 FUCA1 和 NCKAP1L 在非转移性骨肉瘤中显著富集，其高表达与患者生存率的提高相关。基因功能富集主要与免疫功能相关，与巨噬细胞吞噬、抗原呈递和巨噬细胞极化途径呈正相关。免疫微环境分析表明，基因表达与免疫评分呈正相关，高表达组中巨噬细胞、T 细胞和 B 细胞的数量增加。单细胞分析和实验结果证实了 FUCA1 和 NCKAP1L 在巨噬细胞中的富集。
鉴定出 FUCA1 和 NCKAP1L 作为潜在的预后生物标志物，表明它们有改善患者预后的潜力。调节巨噬细胞可能为增强骨肉瘤的免疫微环境提供一种有前途的策略。
