骨肉瘤 (OS) 提出了重大的临床挑战，需要对其分子基础进行全面探索。本研究采用包括 OS 细胞在内的分子实验的多方面方法，探讨了 PTTG 家族基因（PTTG1、PTTG2 和 PTTG3P）在 OS 中的作用品系培养、RT-qPCR、亚硫酸氢盐和全外显子组测序 (WES) 以及计算机模拟实验，包括基于癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据集的验证、总体生存、基因富集、功能测定，以及分子对接分析。我们的研究结果揭示了 OS 细胞系中 PTTG 基因的一致上调，得到 RT-qPCR 实验的支持，并在各种公开可用的表达数据集数据库中得到证实。重要的是，ROC 曲线分析突显了它们作为诊断标志物的潜力。除了表达谱之外，我们还通过证明 OS 中与 PTTG 基因相关的 CpG 岛的显着低甲基化来揭示表观遗传景观。甲基化状态与mRNA表达之间的负相关强调了启动子甲基化在PTTG基因表达中的调节作用。与预期相反，PTTG 基因的基因突变在 OS 中很少见，仅观察到良性突变。此外，功能测定还证实了 PTTG 基因在 OS 发展中的致癌作用。最后，我们还发现骨化三醇是在 PTTG 基因背景下可用于治疗 OS 的最合适药物。PTTG 基因作为潜在诊断标记物的鉴定及其与表观遗传改变的关联为理解 OS 发病机制和开发开辟了新途径。靶向治疗。当我们探索 OS 的复杂格局时，这项研究提供了重要的见解，可能为改进 OS 管理中的诊断和治疗策略铺平道路。版权所有 © 2024 Lu、Wang、Chen、Shan 和 Li。

Osteosarcoma (OS) poses a significant clinical challenge, necessitating a comprehensive exploration of its molecular underpinnings.This study explored the roles of PTTG family genes (PTTG1, PTTG2, and PTTG3P) in OS, employing a multifaceted approach encompassing molecular experiments, including OS cell lines culturing, RT-qPCR, bisulfite and Whole Exome Sequencing (WES) and in silico experiments, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets-based validation, overall survival, gene enrichment, functional assays, and molecular docking analyses.Our findings reveal a consistent up-regulation of PTTG genes in OS cell lines, supported by RT-qPCR experiments and corroborated across various publically available expression datasets databases. Importantly, ROC curve analyses highlight their potential as diagnostic markers. Moving beyond expression profiles, we unveil the epigenetic landscape by demonstrating significant hypomethylation of CpG islands associated with PTTG genes in OS. The negative correlation between methylation status and mRNA expression emphasizes the regulatory role of promoter methylation in PTTG gene expression. Contrary to expectations, genetic mutations in PTTG genes are rare in OS, with only benign mutations observed. Moreover, functional assays also confirmed the oncogenic roles of the PTTG gene in the development of OS. Lastly, we also revealed that Calcitriol is the most appropriate drug that can be utilized to treat OS in the context of PTTG genes.The identification of PTTG genes as potential diagnostic markers and their association with epigenetic alterations opens new avenues for understanding OS pathogenesis and developing targeted therapies. As we navigate the complex landscape of OS, this study contributes essential insights that may pave the way for improved diagnostic and therapeutic strategies in its management.Copyright © 2024 Lu, Wang, Chen, Shan and Li.