Osteosarcoma, known for its rapid progression and high metastatic potential, poses significant challenges in adolescent oncology. This study delves into the roles of lipid metabolism and acetylation genes in the disease's pathogenesis. Utilizing gene set variation analysis, we examined 14 lipid metabolism-related pathways in osteosarcoma patients, identifying significant variances in three pathways between metastatic and primary cases. Additionally, differences in four acetylation genes between these groups were observed. A comprehensive analysis pinpointed 62 lipid metabolism-related genes, with 39 exhibiting significant correlations with acetylation genes, termed lipid metabolism acetylation (LMA) genes. Employing machine learning techniques like Lasso+RSF and GBM, we developed a predictive model for overall survival based on LMA genes. This model, with an average c-index of 0.771, focuses on three key genes: CYP2C8, PAFAH2, and ACOX3, whose prognostic value was confirmed through survival and receiver operating characteristic curve analyses. Quantitative RT-PCR results indicated higher expression levels of ACOX3 and PAFAH2 in OS cells (143B, HOS, MG63) than in osteoblasts (hFOB1.19), while CYP2C8 was lower in OS cells. Furthermore, drug sensitivity analysis through the pRRophetic algorithm suggested potential targeted therapies, revealing drugs with differential sensitivity based on LMA scores and varied treatment responses related to the expression of core genes. This study not only highlights the crucial role of lipid metabolism and acetylation in osteosarcoma but also offers a foundation for personalized treatment strategies, marking a notable advancement in combating this severe form of adolescent cancer.

中文翻译：

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破译脂质代谢和乙酰化在骨肉瘤中的作用：综合分子分析。


骨肉瘤以其快速进展和高转移潜力而闻名，在青少年肿瘤学中构成了重大挑战。本研究深入探讨了脂质代谢和乙酰化基因在疾病发病机制中的作用。利用基因集变异分析，我们检查了骨肉瘤患者的 14 种脂质代谢相关通路，确定了转移性病例和原发性病例之间 3 条通路的显着差异。此外，观察到这些组之间 4 个乙酰化基因的差异。一项综合分析确定了 62 个脂质代谢相关基因，其中 39 个与乙酰化基因（称为脂质代谢乙酰化 （LMA） 基因）表现出显著相关性。采用 Lasso+RSF 和 GBM 等机器学习技术，我们开发了一个基于 LMA 基因的总生存期预测模型。该模型的平均 c 指数为 0.771，侧重于三个关键基因： CYP2C8 、 PAFAH2 和 ACOX3，其预后价值通过生存和受试者工作特征曲线分析得到证实。定量 RT-PCR 结果显示 OS 细胞 （143B、HOS、MG63） 中 ACOX3 和 PAFAH2 的表达水平高于成骨细胞 （hFOB1.19），而 CYP2C8 在 OS 细胞中的表达水平较低。此外，通过 pRRophetic 算法进行的药物敏感性分析表明了潜在的靶向治疗，揭示了基于 LMA 评分的具有不同敏感性的药物以及与核心基因表达相关的不同治疗反应。这项研究不仅强调了脂质代谢和乙酰化在骨肉瘤中的关键作用，还为个性化治疗策略提供了基础，标志着在对抗这种严重形式的青少年癌症方面取得了显着进展。