Abstract
Background: Abnormal expression of lncRNA is closely related to the occurrence and metastasis of osteosarcoma. The tumor immune microenvironment (TIM) is considered to be an important factor affecting the prognosis and treatment of osteosarcoma. This study aims to explore the effect of immune-related lncRNAs (IRLs) on the prognosis of osteosarcoma and its relationship with the TIM.Methods: Ninety-five osteosarcoma samples from the TARGET database were included. Iterative LASSO regression and multivariate Cox regression analysis were used to screen the IRLs signature with the optimal AUC. The predict function was used to calculate the risk score and divide osteosarcoma into a high-risk group and low-risk group based on the optimal cut-off value of the risk score. The lncRNAs in IRLs signature that affect metastasis were screened for in vitro validation. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were used to evaluate the role of TIM in the influence of IRLs on osteosarcoma prognosis.Results: Ten IRLs constituted the IRLs signature, with an AUC of 0.96. The recurrence and metastasis rates of osteosarcoma in the high-risk group were higher than those in the low-risk group. In vitro experiments showed that knockdown of lncRNA (AC006033.2) could increase the proliferation, migration, and invasion of osteosarcoma. ssGSEA and ESTIMATE results showed that the immune cell content and immune score in the low-risk group were generally higher than those in the high-risk group. In addition, the expression levels of immune escape-related genes were higher in the high-risk group.Conclusion: The IRLs signature is a reliable biomarker for the prognosis of osteosarcoma, and they alter the prognosis of osteosarcoma. In addition, IRLs signature and patient prognosis may be related to TIM in osteosarcoma. The higher the content of immune cells in the TIM of osteosarcoma, the lower the risk score of patients and the better the prognosis. The higher the expression of immune escape-related genes, the lower the risk score of patients and the better the prognosis.
Highlights
Osteosarcoma is the most common primary malignant bone tumor, most commonly occurring in adolescents and children (Huang et al, 2021)
Through 1000 iterations, a total of 11 lncRNAs with a frequency greater than 300 were screened out. These lncRNAs were incorporated into the Cox regression analysis one by one until the AUC value of immune-related lncRNAs (IRLs) signature reached the maximum
Correlation analysis was conducted between all lncRNAs and the gene set (IMMUNE RESPONSE TO TUMOR CELL), and 4986 IRLs were obtained (Supplementary Table 4)
Summary
Osteosarcoma is the most common primary malignant bone tumor, most commonly occurring in adolescents and children (Huang et al, 2021). Osteosarcoma has the characteristics of high malignancy, rapid growth, and easy metastasis. Pulmonary metastasis is one of the major factors leading to the poor prognosis of osteosarcoma, and more than 20% of patients with osteosarcoma have had pulmonary metastasis at the time of diagnosis (Anderson, 2016). It is important to clarify the causes and mechanisms affecting the prognosis of osteosarcoma to prolong the survival time of osteosarcoma. Abnormal expression of lncRNA is closely related to the occurrence and metastasis of osteosarcoma. The tumor immune microenvironment (TIM) is considered to be an important factor affecting the prognosis and treatment of osteosarcoma. This study aims to explore the effect of immune-related lncRNAs (IRLs) on the prognosis of osteosarcoma and its relationship with the TIM
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