背景：骨肉瘤（OS）是一种原发性恶性骨肿瘤，面临多药耐药的治疗挑战。对疾病的发生和进展进行全面的理解对于推进治疗策略至关重要。m7G修饰是一种新兴的转录后修饰，在各种疾病中起着重要作用，可能为探索OS的发病机制和进展提供新的观点。方法：利用多样的生物信息学分析方法，包括LASSO Cox回归、免疫浸润评估和药物敏感性分析，探索OS中与m7G相关的分子景观。此外，通过细胞凋亡和周期实验研究了AZD2014对OS的治疗潜力。最后，进行多变量Cox分析和实验证实，以探讨独立的与m7G相关的预后基因。结果：建立了一个包含八个标志的全面的与m7G相关的风险模型，相应的风险评分与免疫浸润和药物敏感性相关。药物敏感性分析将AZD2014视为OS的潜在治疗候选药物。随后的实验证实了AZD2014诱导OS细胞G1期细胞周期阻滞和凋亡的能力。最终，多变量Cox回归分析揭示了CYFIP1和EIF4A1的独立预后重要性，它们的差异表达在组织和细胞水平上得到了验证。结论：本研究深入了解了m7G相关基因对OS发病机制的贡献。AZD2014的治疗潜力以及CYFIP1和EIF4A1被确定为独立的危险因素开启了OS治疗的新视野。版权所有©2023 Lin、Wu、Yuan、Zhong和Luo.

Background: Osteosarcoma (OS), a primary malignant bone tumor, confronts therapeutic challenges rooted in multidrug resistance. Comprehensive understanding of disease occurrence and progression is imperative for advancing treatment strategies. m7G modification, an emerging post-transcriptional modification implicated in various diseases, may provide new insights to explore OS pathogenesis and progression. Methods: The m7G-related molecular landscape in OS was probed using diverse bioinformatics analyses, encompassing LASSO Cox regression, immune infiltration assessment, and drug sensitivity analysis. Furthermore, the therapeutic potential of AZD2014 for OS was investigated through cell apoptosis and cycle assays. Eventually, multivariate Cox analysis and experimental validations, were conducted to investigate the independent prognostic m7G-related genes. Results: A comprehensive m7G-related risk model incorporating eight signatures was established, with corresponding risk scores correlated with immune infiltration and drug sensitivity. Drug sensitivity analysis spotlighted AZD2014 as a potential therapeutic candidate for OS. Subsequent experiments corroborated AZD2014's capability to induce G1-phase cell cycle arrest and apoptosis in OS cells. Ultimately, multivariate Cox regression analysis unveiled the independent prognostic importance of CYFIP1 and EIF4A1, differential expressions of which were validated at histological and cytological levels. Conclusion: This study furnishes a profound understanding of the contribution of m7G-related genes to the pathogenesis of OS. The discerned therapeutic potential of AZD2014, in conjunction with the identification of CYFIP1 and EIF4A1 as independent risk factors, opens novel vistas for the treatment of OS.Copyright © 2023 Lin, Wu, Yuan, Zhong and Luo.