Integrated analyses of an RNA binding protein-based signature related to tumor immune microenvironment and candidate drugs in osteosarcoma.

OBJECTIVE: Osteosarcoma is the most frequent primary bone malignancy, associated with frequent recurrence and lung metastasis. RNA-binding proteins (RBPs) are pivotal in regulating several aspects of cancer biology. Nonetheless, interaction between RBPs and the osteosarcoma immune microenvironment is poorly understood. We investigated whether RBPs can predict prognosis and immunotherapy response in osteosarcoma patients.
METHODS: We constructed an RBP-related prognostic signature (RRPS) by univariate coupled with multivariate analyses and verified the independent prognostic efficacy of the signature. Single-sample Gene Set Enrichment Analysis (ssGSEA) along with ESTIMATE analysis were carried out to investigate the variations in immune characteristics between subgroups with various RRPS-scores. Furthermore, we investigatedpossible small molecule drugs using the connectivity map database and validated the expression of hub RBPs by qRT-PCR.
RESULTS: The RRPS, consisting of seven hub RBPs, was an independent prognostic factor compared to traditional clinical features. The RRPS could distinguish immune functions, immune score, stromal score, tumor purity and tumor infiltration by immune cells in different osteosarcoma subjects. Additionally, patients with high RRPS-scores had lower expression of immune checkpoint genes than patients with low RRPS-scores. We finally identified six small molecule drugs that may improve prognosis in osteosarcoma patients and substantiated notable differences in the contents of these RBPs.
CONCLUSION: We evaluated the prognostic value and clinical application of an RBPs-based prognostic signature and identified promising biomarkers to predict immune cell infiltration and immunotherapy response in osteosarcoma. AJTR