Osteosarcoma is a highly aggressive cancer prevalent among adolescents and young adults, notorious for its tendency to metastasize to the lungs. This research delves into the molecular foundations of osteosarcoma by examining the role of the Hippo signaling pathway and its interaction with the tumor immune microenvironment (TME). Through analysis of transcriptomic data from the TARGET‐OS dataset and control samples from GTEx, we identified a set of 131 genes that link high expression profiles in osteosarcoma with the Hippo pathway. A focused examination through univariate Cox regression analysis revealed eight key genes (DLG5, WNT11, TGFB2, DLG4, WNT16, ID2, WNT10B, and WNT10A) with a significant correlation to patient outcomes. Hierarchical clustering of these genes delineated two distinct patient groups with significantly different survival rates, a finding supported by Kaplan–Meier survival analysis. Further investigation into immune cell infiltration and expression profiles of immunoregulatory factors uncovered a notable pattern of immune evasion in the group with poorer prognosis, marked by reduced effector immune cell activity and lower levels of immunostimulatory factors. Single‐cell sequencing highlighted the cellular diversity within osteosarcoma samples and identified markers differentiating malignant from nonmalignant cells, correlating these markers with prognostic risk scores. Our results emphasize the critical prognostic value of Hippo pathway genes and the TME in osteosarcoma, shedding light on new avenues for therapeutic intervention and patient‐specific treatment strategies.

中文翻译：

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解读骨肉瘤的预后情况：整合河马通路基因、程序性细胞死亡和肿瘤免疫微环境的作用

骨肉瘤是一种在青少年和年轻人中流行的高度侵袭性癌症，因其容易转移至肺部而臭名昭著。这项研究通过检查 Hippo 信号通路的作用及其与肿瘤免疫微环境 (TME) 的相互作用，深入探讨了骨肉瘤的分子基础。通过分析 TARGET-OS 数据集的转录组数据和 GTEx 的对照样本，我们确定了一组 131 个基因，这些基因将骨肉瘤中的高表达谱与 Hippo 通路联系起来。通过单变量 Cox 回归分析进行的集中检查揭示了八个关键基因（DLG5、WNT11、TGFB2、DLG4、WNT16、ID2、WNT10B 和 WNT10A）与患者结果显着相关。这些基因的层次聚类描绘了两个不同的患者群体，其生存率显着不同，这一发现得到了卡普兰-迈耶生存分析的支持。对免疫细胞浸润和免疫调节因子表达谱的进一步研究发现，预后较差的人群存在显着的免疫逃避模式，其特点是效应免疫细胞活性降低和免疫刺激因子水平较低。单细胞测序强调了骨肉瘤样本中的细胞多样性，并确定了区分恶性细胞和非恶性细胞的标记，将这些标记与预后风险评分相关联。我们的结果强调了 Hippo 通路基因和 TME 在骨肉瘤中的关键预后价值，为治疗干预和患者特异性治疗策略的新途径提供了线索。