Potential predictive value of immune-related genes FUCA1 and NCKAP1L for osteosarcoma metastasis

Abstract

BackgroundOsteosarcoma is a common malignant tumor with a low survival rate after metastasis. Current treatments have not proven to effectively increase patient survival rates. Immunotherapy is a promising new treatment approach, however, immune target therapy has not shown satisfactory results. This study aims to provide new insights and evidence for the use of immunotherapy in osteosarcoma, based on a comprehensive analysis of gene expression data from databases. MethodsGene expression and GSAV analysis were conducted on samples from patients with metastatic and non-metastatic osteosarcoma in the TARGET and GEO databases to identify relevant genes. These genes were further analyzed using GO, KEGG, GSVA, correlation analysis, and immune microenvironment scoring techniques. The tissue location of gene expression was confirmed through single-cell analysis. Validation of gene expression patterns was performed using polymerase chain reaction, western blot, and immunohistochemistry. ResultsThe study identified FUCA1 and NCKAP1L as significantly enriched in non-metastatic osteosarcoma, with higher expression associated with better patient survival rates. Gene function enrichment was primarily related to immune functions, with positive correlations to macrophage phagocytosis, antigen presentation, and macrophage polarization pathways. Analysis of the immune microenvironment revealed a positive correlation between gene expression and immune scores, with increased presence of macrophages, T cells, and B cells in the high expression group. Single-cell analysis and experimental results confirmed the enrichment of FUCA1 and NCKAP1L in macrophages. ConclusionThe identification of FUCA1 and NCKAP1L as potential prognostic biomarkers suggests their potential for improving patient outcomes. Modulation of macrophages may offer a promising strategy for enhancing the immune microenvironment in osteosarcoma.