Department of Orthopedic Surgery, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, P. R. China.
Faculty of Medical Science, Kunming University of Science and Technology, Kunming, P. R. China.
Toxicol Mech Methods. 2023 Nov;33(9):781-795. doi: 10.1080/15376516.2023.2240879. Epub 2023 Aug 8.
This study identified and verified the characteristic differentially expressed ferroptosis-related genes (CDEFRGs) in osteosarcoma (OS).
We extracted ferroptosis-related genes (FRGs), identified differentially expressed FRGs (DEFRGs) in OS, and conducted correlation analysis between DEFRGs. Next, we conducted GO and KEGG analyses to explore the biological functions and pathways of DEFRGs. Furthermore, we used LASSO and SVM-RFE algorithms to screen CDEFRGs, and evaluated its accuracy in diagnosing OS through ROC curves. Then, we demonstrated the molecular function and pathway enrichment of CDEFRGs through GSEA analysis. In addition, we evaluated the differences in immune cell infiltration between OS and NC groups, as well as the correlation between CDEFRGs expressions and immune cell infiltrations. Finally, the expression of CDEFRGs was verified through qRT-PCR, western blotting, and immunohistochemistry experiments.
We identified 51 DEFRGs and the expression relationship between them. GO and KEGG analysis revealed their key functions and important pathways. Based on four CDEFRGs (, , , and ), we built the OS diagnostic model, and verified its accuracy. GSEA analysis further revealed the important functions and pathways of CDEFRGs. In addition, there were differences in immune cell infiltration between OS group and NC group, and CDEFRGs showed significant correlation with certain infiltrating immune cells. Finally, we validated the differential expression levels of four CDEFRGs through external experiments.
This study has shed light on the molecular pathological mechanism of OS and has offered novel perspectives for the early diagnosis and immune-targeted therapy of OS patients.
本研究鉴定并验证了骨肉瘤（OS）中特征性差异表达的铁死亡相关基因（CDEFRGs）。
我们提取了铁死亡相关基因（FRGs），鉴定了 OS 中差异表达的 FRGs（DEFRGs），并对 DEFRGs 进行了相关性分析。接着，我们进行了 GO 和 KEGG 分析，以探讨 DEFRGs 的生物学功能和通路。此外，我们使用 LASSO 和 SVM-RFE 算法筛选 CDEFRGs，并通过 ROC 曲线评估其诊断 OS 的准确性。然后，我们通过 GSEA 分析展示了 CDEFRGs 的分子功能和通路富集。另外，我们评估了 OS 组和 NC 组之间免疫细胞浸润的差异，以及 CDEFRGs 表达与免疫细胞浸润的相关性。最后，通过 qRT-PCR、western blot 和免疫组化实验验证了 CDEFRGs 的表达。
我们鉴定了 51 个 DEFRGs 及其表达关系。GO 和 KEGG 分析揭示了它们的关键功能和重要通路。基于 4 个 CDEFRGs（、、、和），我们构建了 OS 诊断模型，并验证了其准确性。GSEA 分析进一步揭示了 CDEFRGs 的重要功能和通路。此外，OS 组和 NC 组之间存在免疫细胞浸润的差异，CDEFRGs 与某些浸润免疫细胞显著相关。最后，我们通过外部实验验证了 4 个 CDEFRGs 的差异表达水平。
本研究揭示了 OS 的分子病理机制，为 OS 患者的早期诊断和免疫靶向治疗提供了新的视角。
