Discovery of New Therapeutic Targets for Osteosarcoma Treatment Based on Immune-Related lncRNAs in the Tumor Microenvironment

BACKGROUND: Long noncoding RNAs (lncRNAs) play an important role in osteosarcoma development, but their role in the tumor microenvironment (TME) is not fully understood. This study associated lncRNAs with immune-related genes and explored the mechanism of lncRNAs in osteosarcoma progression. METHODS: Unsupervised consensus clustering was applied to construct immune subtypes based on immune-related lncRNAs identified by Pearson's correlation analysis. A series of functional analysis was performed to reveal the links among lncRNAs, immune subtypes, TME, and osteosarcoma prognosis. RESULTS: We identified two immune subtypes C1 and C2 showing distinct overall survival. ECM-receptor interaction pathway was more activated in C2 subtype, while immune response pathways were more enriched in C2 subtype. Differential TME and response to chemotherapeutic drugs were observed between the two subtypes. Four metagenes of costimulation, cytolytic activity (CYT), immune score, and STAT1 were differentially enriched in the two subtypes. Based on 26-paired lncRNAs, we constructed a 4-paired lncRNA prognostic signature for predicting prognosis of osteosarcoma prognosis. CONCLUSIONS: This study focused on immune-related lncRNAs and TME, showing the possible role and mechanisms of lncRNAs in tumor growth and metastasis. ECM may be the new therapeutic target for treating osteosarcoma, and 26-paired lncRNAs could serve as a basis for further studying the mechanisms of CYT and STAT1 in immune response, cancer cell proliferation, and migration. The two subtypes and prognostic signature could promote the design of personalized osteosarcoma treatment.