Screening a novel signature and predicting the immune landscape of metastatic osteosarcoma in children via immune-related lncRNAs.

Background: The immune microenvironment plays an essential role in osteosarcoma (OSs); however, differences in immune-related long non-coding ribonucleic acids (irlncRNAs) in children with localized OSs and metastatic OSs have not yet been investigated.

Methods: The clinical data and the transcriptome of OSs were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and the immune-related genes were derived from the imported dataset. The correlations between immune-related genes and lncRNAs were examined. Next, the differential expressions of the irlncRNA pairs (IRLPs) in localized OSs and distant metastatic OSs were analyzed, and a prognostic model was constructed based on the significant differentially expressed IRLPs. We also analyzed the association between the IRLPs' signature risk score and the infiltration of the immune cells. Finally, we investigated the correlation between risk score and drug resistance.

Results: Thirty upregulated and 22 downregulated lncRNAs were identified in the localized and metastatic OSs samples. Univariate and multivariate cox regression analyses were undertaken to select 6 lncRNA pairs to establish the prognostic signature, the model was valuable in predicting OSs prognosis. Further, the expression of the finally selected irlncRNAs indicated that VPS9D1-AS1 (P=0.031), AP003086.2 (P=0.041), AL031847.1 (P=0.008), AL020997.3 (P=0.020), AC011444.1 (P=0.025), and AC006449.2 (P=0.003) were significantly upregulated in metastasis patients, but USP27X-AS1 (P=0.046), AL008721.2 (P=0.005), AC002091.1 (P=0.033), and AL118558.4 (P=0.049) were significantly overexpressed in localized patients. The overexpression of AC002091.1 (P=0.038) and AL118558.4 (P=0.004) resulted in better overall survival, but the upregulation of AC011444.1 (P=0.045), AL031847.1 (P=0.020), VPS9D1-AS1 (P=0.039), and AC006449.2 (0.006) led to a poor outcome. Differences in immune cell infiltration indicated that metastatic patients and localized have significant difference of 4 (CD4) T cells (P=0.006), monocytes (P=0.029), activated mast cells (P=0.018), and neutrophils (P=0.026), and a high abundance of activated dendritic cells (P=0.010) and activated mast cells (P=0.049) resulted in poor prognosis. Patients in the high-risk-score group were resistant to axitinib, but sensitive to dasatinib, bortezomib, and cisplatin.

Conclusions: In the present study, IRLPs were used to construct a novel and practical model for predicting the prognosis of localized and metastatic OSs in children.