Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Biochem Genet. 2024 Apr;62(2):831-852. doi: 10.1007/s10528-023-10446-1. Epub 2023 Jul 17.
Osteosarcoma (OS) is a frequent primary malignant bone tumor, with a poor prognosis. Necroptosis is strongly correlated with OS and may be an influential target for treating OS. This study's objective was to establish a necroptosis-related gene (NRG) prognostic signature that could predict OS prognosis and guide OS treatment. First, we identified 20 NRGs associated with OS survival based on the TARGET database. We then derived a 7 NRG prognostic signature. Our findings revealed that the 7 NRG prognostic signature performed well in predicting the survival of OS patients. We next analyzed differences in immunological status and immune cell infiltration. In addition, we examined the relationship between chemo/immunotherapeutic response and the 7-NRG prognostic signature. In addition, to probe the mechanisms underlying the NRG prognostic signature, we performed functional enrichment assays including GO and KEGG. Finally, CHMP4C was selected for functional experiments. Silencing CHMP4C prevented OS cells from proliferating, migrating, and invading. This 7-NRG prognostic signature seems to be an excellent predictor that can provide a fresh direction for OS treatment.
骨肉瘤（OS）是一种常见的原发性恶性骨肿瘤，预后不良。细胞坏死性凋亡与 OS 密切相关，可能是治疗 OS 的一个有影响力的靶点。本研究的目的是建立一个与细胞坏死性凋亡相关的基因（NRG）预后标志，以预测 OS 的预后并指导 OS 的治疗。首先，我们根据 TARGET 数据库鉴定了 20 个与 OS 生存相关的 NRG。然后，我们推导出了一个 7 NRG 预后标志。我们的研究结果表明，该 7 NRG 预后标志在预测 OS 患者的生存方面表现良好。接下来，我们分析了免疫状态和免疫细胞浸润的差异。此外，我们还研究了化疗/免疫治疗反应与 7-NRG 预后标志之间的关系。此外，为了探究 NRG 预后标志的潜在机制，我们进行了包括 GO 和 KEGG 在内的功能富集分析。最后，选择 CHMP4C 进行功能实验。沉默 CHMP4C 可阻止 OS 细胞的增殖、迁移和侵袭。这个 7-NRG 预后标志似乎是一个优秀的预测因子，可以为 OS 的治疗提供新的方向。
