Background: Necroptosis is closely related to tumorigenesis and development. Accumulating evidence has revealed that long non-coding RNAs (lncRNAs) are also central players in osteosarcoma (OS). However, the role of necroptosis-related lncRNAs in OS remains unclear. In the present study, we aim to craft a prognostic signature based on necroptosis-related lncRNAs to improve the OS prognosis prediction. Methods: The signature based on necroptosis-related lncRNAs was discovered using univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. The prognosis efficiency of the signature was then estimated by employing various bioinformatics methods. Subsequently, immunological analysis and Gene Set Enrichment Analysis (GSEA) were used to explore the association between necroptosis-related lncRNAs with clinical outcomes and immune status. More importantly, several necroptosis-related lncRNAs were validated with RT-qPCR. Results: Consequently, a novel prognosis signature was successfully constructed based on eight necroptosis-related lncRNAs. Meanwhile, the novel necroptosis-related lncRNAs model could distribute OS patients into two risk groups with a stable and accurate predictive ability. Additionally, the GSEA and immune analysis revealed that the necroptosis-related lncRNAs signature affects the development and prognosis of OS by regulating the immune status. The necroptosis-related lncRNA signature was closely correlated with multiple anticancer agent susceptibility. Moreover, the RT-qPCR results indicated several necroptosis-related lncRNAs were significantly differently expressed in osteosarcoma and osteoblast cell lines. Conclusion: In this summary, a novel prognostic signature integrating necroptosis-related lncRNAs was firstly constructed and could accurately predict the prognosis of OS. This study may increase the predicted value and guide the personalized chemotherapy treatment for OS.

中文翻译：

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一种新的坏死性凋亡相关 lncRNAs 特征可有效预测骨肉瘤的预后并与免疫相关。

背景：坏死性凋亡与肿瘤的发生、发展密切相关。越来越多的证据表明，长链非编码 RNA (lncRNA) 也是骨肉瘤 (OS) 的核心参与者。然而，坏死性凋亡相关 lncRNA 在 OS 中的作用仍不清楚。在本研究中，我们旨在基于坏死性凋亡相关的 lncRNA 构建预后特征，以改善 OS 预后预测。方法：使用单变量 Cox、最小绝对收缩和选择算子 (LASSO) 和多变量 Cox 回归分析发现基于坏死性凋亡相关 lncRNA 的特征。然后通过采用各种生物信息学方法估计特征的预后效率。随后，免疫学分析和基因集富集分析（GSEA）用于探索坏死性凋亡相关lncRNA与临床结果和免疫状态之间的关联。更重要的是，用 RT-qPCR 验证了几种与坏死性凋亡相关的 lncRNA。结果：因此，基于八种坏死性凋亡相关的 lncRNA 成功构建了一种新的预后特征。同时，新的坏死性凋亡相关lncRNAs模型可以将OS患者分为两个风险组，具有稳定和准确的预测能力。此外，GSEA 和免疫分析表明，坏死性凋亡相关的 lncRNAs 特征通过调节免疫状态影响 OS 的发展和预后。坏死性凋亡相关的 lncRNA 特征与多种抗癌药物的敏感性密切相关。而且，RT-qPCR 结果表明，几种坏死性凋亡相关的 lncRNA 在骨肉瘤和成骨细胞系中的表达存在显着差异。结论：在本综述中，首次构建了一种整合坏死性凋亡相关 lncRNA 的新型预后特征，可以准确预测 OS 的预后。本研究可提高预测值，指导OS个体化化疗治疗。