A novel necroptosis-related lncRNAs signature effectively predicts the prognosis for osteosarcoma and is associated with immunity

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.

Integrative analysis of TROAP with molecular features, carcinogenesis, and related immune and pharmacogenomic characteristics in soft tissue sarcoma

“…It is well known that the prognosis of cancer is often related to multiple risk factors. A nomogram is a powerful tool for quantifying an individual's risk in a clinical setting by integrating various risk factors 23,24 . Therefore, we used the nomogram to predict 1‐, 3‐, and 5‐year OS probabilities by combining patient age, metastatic status, and a TROAP‐derived signature.…”

“…A nomogram is a powerful tool for quantifying an individual's risk in a clinical setting by integrating various risk factors. 23 , 24 Therefore, we used the nomogram to predict 1‐, 3‐, and 5‐year OS probabilities by combining patient age, metastatic status, and a TROAP‐derived signature. Importantly, ROC curves also indicate the robust efficiency of the nomogram in predicting the clinical outcome of STS individuals.…”

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

“…Necroptosis is a type of PCD that relies on three core proteins, receptor‐interacting protein kinase 1(RIPK1), receptor‐interacting protein 3 (RIP3), and mixed lineage kinase‐like protein (MLKL), to cause organelle swelling and alter the permeability of the cell membrane. 92 Like other PCDs, necrotic apoptosis has a crucial role in the development of osteosarcoma. RIP1 plays a crucial role in necroptosis, TRA/GO reduces cIAP and Caspase‐8, the reduction of cIAP contributes to the formation of intracellular platform complexes, whereas the decrease in Caspase‐8 activity facilitates the formation of RIP1/RIP3/MLKL complexes, which promotes necroptosis and kills osteosarcoma cells.…”

“…Necrotic apoptosis‐related lncRNAs can also affect OS by influencing immunity. 92 Shikonin (SHK) can promote the RIP1 and RIP3‐dependent necroptosis to treat osteosarcoma. 98 , 99 As one of the most common kinds of necroptosis, the TNF‐mediated necroptosis is induced by the binding between TNF‐α and cell membrane, which can activate the downstream signal pathway leading to the formation of membrane complex and this can lead to necroptosis.…”

“…Necroptosis is a type of PCD that relies on three core proteins, receptor‐interacting protein kinase 1(RIPK1), receptor‐interacting protein 3 (RIP3), and mixed lineage kinase‐like protein (MLKL), to cause organelle swelling and alter the permeability of the cell membrane 92 . Like other PCDs, necrotic apoptosis has a crucial role in the development of osteosarcoma.…”