Liu Binfeng, Feng Chengyao, Liu Zhongyue, Tu Chao, Li Zhihong
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Front Pharmacol. 2022 Aug 29;13:944158. doi: 10.3389/fphar.2022.944158. eCollection 2022.
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. 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. 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. 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.
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（lncRNAs）在骨肉瘤（OS）中也起着关键作用。然而，与坏死性凋亡相关的lncRNAs在OS中的作用仍不清楚。在本研究中，我们旨在构建一个基于坏死性凋亡相关lncRNAs的预后特征，以改善OS预后预测。使用单因素Cox、最小绝对收缩和选择算子（LASSO）以及多因素Cox回归分析发现了基于坏死性凋亡相关lncRNAs的特征。然后采用各种生物信息学方法评估该特征的预后效率。随后，通过免疫分析和基因集富集分析（GSEA）来探讨坏死性凋亡相关lncRNAs与临床结局和免疫状态之间的关联。更重要的是，通过RT-qPCR验证了几种与坏死性凋亡相关的lncRNAs。因此，成功构建了一个基于8个坏死性凋亡相关lncRNAs的新型预后特征。同时，新型坏死性凋亡相关lncRNAs模型可将OS患者分为两个风险组，具有稳定且准确的预测能力。此外，GSEA和免疫分析表明，坏死性凋亡相关lncRNAs特征通过调节免疫状态影响OS的发生发展和预后。坏死性凋亡相关lncRNA特征与多种抗癌药物敏感性密切相关。此外，RT-qPCR结果表明，几种坏死性凋亡相关lncRNAs在骨肉瘤和成骨细胞系中的表达存在显著差异。综上所述，首次构建了一个整合坏死性凋亡相关lncRNAs的新型预后特征，可准确预测OS的预后。本研究可能会提高预测价值，并指导OS的个体化化疗治疗。
