A mitochondria-related signature for predicting immune microenvironment and therapeutic response in osteosarcoma

BACKGROUND: Osteosarcoma remains to be the most devastating malignant tumor in children and teenagers. Mitochondria have also been proven to play critical roles in osteosarcoma. However, a mitochondria-related signature has been established in osteosarcoma to comprehensively evaluate the pathogenic roles and regulatory roles of mitochondria in osteosarcoma. METHODS: In this study, osteosarcoma samples' transcriptome data and clinical information were collected from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. A comprehensive bioinformatics analysis was performed on the samples at the bulk RNA sequencing level and single-cell RNA sequencing (scRNA-seq) level. EdU, Transwell, and immunohistochemistry (IHC) were performed on PCCB. RESULTS: A mitochondria-related signature was constructed in osteosarcoma patients. The prognostic value of the mitochondria-related signature was explored. The predictive value of the mitochondria-related signature in the immune microenvironment and chemotherapy agents was explored. The association between mitochondria and immunity in the tumor microenvironment of osteosarcoma at the scRNA-seq level was investigated. The tumorigenic role of the critical mitochondria-related gene, PCCB, was verified by in vitro validation. CONCLUSION: In conclusion, a mitochondria-related signature was developed in osteosarcoma with solid predictive values in the immune microenvironment, chemotherapy agents, and prognosis.