Abstract

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.