Research on the implications of ferroptosis in tumors has increased rapidly in the last decades. There are evidences that ferroptosis is involved in several aspects of cancer biology, including tumor progression, metastasis, immunomodulation, and therapeutic response. Nonetheless, the interaction between ferroptosis-related lncRNAs (FRLs) and the osteosarcoma immune microenvironment is poorly understood. In this study, a risk model composed of FRLs was developed using univariate and LASSO Cox regression analyses. On the basis of this model, FRL scores were calculated to systematically explore the role of the model in predicting the prognosis and immune characteristics of osteosarcoma patients. Survival analysis showed that osteosarcoma samples with lower FRL-score had better overall survival. After predicting the abundance of immune cells in osteosarcoma microenvironment by single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE analysis, we found that the FRL-score could distinguish immune function, immune score, stromal score, tumor purity, and tumor infiltration of immune cells in different osteosarcoma patients. In addition, FRL-score was also associated with immune checkpoint gene expression and half-maximal inhibitory concentration of chemotherapeutic agents. Finally, we confirmed that knockdown of RPARP-AS1 suppressed the malignant activity of osteosarcoma cells in vitro experiments. In general, the FRL-based prognostic signature could promote our understanding of the immune microenvironment characteristics of osteosarcoma and guide more effective treatment regimens.

在过去的几十年里，关于铁死亡对肿瘤的影响的研究迅速增加。有证据表明，铁死亡与癌症生物学的多个方面有关，包括肿瘤进展、转移、免疫调节和治疗反应。尽管如此，人们对铁死亡相关的 lncRNA (FRL) 与骨肉瘤免疫微环境之间的相互作用知之甚少。在这项研究中，使用单变量和 LASSO Cox 回归分析开发了一个由 FRL 组成的风险模型。在该模型的基础上，计算FRL评分，系统探讨该模型在预测骨肉瘤患者预后和免疫特征方面的作用。生存分析表明，具有较低 FRL 评分的骨肉瘤样本具有更好的总体生存率。通过单样本基因集富集分析（ssGSEA）和ESTIMATE分析预测骨肉瘤微环境中免疫细胞的丰度后，我们发现FRL-score可以区分免疫功能、免疫评分、基质评分、肿瘤纯度和肿瘤浸润不同骨肉瘤患者的免疫细胞。此外，FRL 评分还与免疫检查点基因表达和化疗药物的半数最大抑制浓度相关。最后，我们证实了 RPARP-AS1 的敲低抑制了骨肉瘤细胞的恶性活动 和不同骨肉瘤患者中免疫细胞的肿瘤浸润。此外，FRL 评分还与免疫检查点基因表达和化疗药物的半数最大抑制浓度相关。最后，我们证实了 RPARP-AS1 的敲低抑制了骨肉瘤细胞的恶性活动 和不同骨肉瘤患者中免疫细胞的肿瘤浸润。此外，FRL 评分还与免疫检查点基因表达和化疗药物的半数最大抑制浓度相关。最后，我们证实了 RPARP-AS1 的敲低抑制了骨肉瘤细胞的恶性活动体外实验。一般来说，基于 FRL 的预后特征可以促进我们对骨肉瘤免疫微环境特征的理解，并指导更有效的治疗方案。