Osteosarcoma (OS) is a cancer that is frequently found in children and adolescents and has made little improvement in terms of prognosis in recent years. A recently discovered type of programmed cell death called cuproptosis is mediated by copper ions and the tricarboxylic acid (TCA) cycle. The expression patterns, roles, and prognostic and predictive capabilities of the cuproptosis regulating genes were investigated in this work. TARGET and GEO provided transcriptional profiling of OS. To find different cuproptosis gene expression patterns, consensus clustering was used. To identify hub genes linked to cuproptosis, differential expression (DE) and weighted gene co-expression network analysis (WGCNA) were used. Cox regression and Random Survival Forest were used to build an evaluation model for prognosis. For various clusters/subgroups, GSVA, mRNAsi, and other immune infiltration experiments were carried out. The drug-responsive study was carried out by the Oncopredict algorithm. Cuproptosis genes displayed two unique patterns of expression, and high expression of FDX1 was associated with a poor outcome in OS patients. The TCA cycle and other tumor-promoting pathways were validated by the functional study, and activation of the cuproptosis genes may also be connected with immunosuppressive state. The robust survival prediction ability of a five-gene prognostic model was verified. This rating method also took stemness and immunosuppressive characteristics into account. Additionally, it can be associated with a higher sensitivity to medications that block PI3K/AKT/mTOR signaling as well as numerous chemoresistances. U2OS cell migration and proliferation may be encouraged by PLCD3. The relevance of PLCD3 in immunotherapy prediction was verified. The prognostic significance, expressing patterns, and functions of cuproptosis in OS were revealed in this work on a preliminary basis. The cuproptosis-related scoring model worked well for predicting prognosis and chemoresistance.

中文翻译：

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Cuproptosis 特征和 PLCD3 预测骨肉瘤的免疫浸润和药物反应

骨肉瘤（OS）是一种常见于儿童和青少年的癌症，近年来在预后方面几乎没有改善。最近发现的一种称为铜细胞凋亡的程序性细胞死亡是由铜离子和三羧酸 (TCA) 循环介导的。在这项工作中研究了铜凋亡调节基因的表达模式、作用以及预后和预测能力。TARGET 和 GEO 提供了 OS 的转录分析。为了找到不同的 cuproptosis 基因表达模式，使用了共识聚类。为了鉴定与铜细胞凋亡相关的中枢基因，使用了差异表达 (DE) 和加权基因共表达网络分析 (WGCNA)。Cox回归和随机生存森林用于建立预后评估模型。对于各种集群/子组，GSVA，进行了mRNAsi等免疫浸润实验。药物反应性研究是通过 Oncopredict 算法进行的。Cuproptosis 基因显示出两种独特的表达模式，FDX1 的高表达与 OS 患者的不良预后相关。TCA循环和其他肿瘤促进途径通过功能研究得到验证，铜凋亡基因的激活也可能与免疫抑制状态有关。验证了五基因预后模型的稳健生存预测能力。这种评级方法还考虑了干性和免疫抑制特性。此外，它可能与阻断 PI3K/AKT/mTOR 信号传导的药物以及许多化学抗性的更高敏感性有关。PLCD3 可能会促进 U2OS 细胞迁移和增殖。验证了 PLCD3 在免疫治疗预测中的相关性。本研究初步揭示了铜细胞凋亡在 OS 中的预后意义、表达模式和功能。铜细胞凋亡相关评分模型在预测预后和化疗耐药性方面效果很好。