骨肉瘤是一种影响青少年和年轻成年人的原发性恶性骨肿瘤。本研究旨在确定能够区分不同骨肉瘤亚型的蛋白质组学特征，为了解其分子异质性以及潜在的个体化治疗方法提供见解。利用先进的蛋白质组学技术，我们分析了来自儿童骨肉瘤患者队列的FFPE肿瘤样本，涵盖了四个不同的亚型。差异表达分析揭示了能够区分这些亚型的显著蛋白质组学特征，突显了与不同肿瘤特征相关的不同分子特征。与此相反，临床决定因素与儿童骨肉瘤的蛋白质组学特征无相关性。鉴定的蛋白质组学特征涵盖了多种参与聚焦粘附、细胞外基质受体相互作用、PI3K-Akt信号通路和癌症中的蛋白聚糖的蛋白质，是富集通路中的顶级。这些发现强调了在诊断或开发个体化治疗策略时考虑骨肉瘤的分子异质性的重要性。通过确定亚型特异蛋白质组学特征，临床医生可以根据个体患者来调整治疗方案，优化治疗效果并减少不良反应。

Osteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.