Identification of differentially expressed immune receptor genes in osteosarcoma

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumour, with a high incidence rate in children and adolescents. However, knowledge surrounding the underlying mechanism(s) and novel therapeutics, require better overall understanding. One important area in need of further exploration is the tumour microenvironment, which consists of a plethora of extracellular matrix components, tumour associated fibroblasts and immune cells. To identify new druggable targets, we searched an OS gene microarray dataset deposited within the Gene Expression Omnibus, which included 84 primary OS biopsies and 12 primary Mesenchymal stem cell control samples. An alternative to R coding was utilised to identify differentially expressed genes (DEGs) in OS. The web tool (GEO2R) utilises the Bioconductor “limma” package to determine DEGs. In addition, R-coding with the ‘Weighted Gene Co‑expression Network Analysis’ package, was used to construct a weighted gene co‑expression network, thus, identifying gene modules associated with OS. Functional annotations were conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes overrepresentation analyses. Upregulated genes were additionally refined, based on the GO term “immune receptor activity”. The results identified 267 DEGs in OS, consisting of 142 upregulated and 125 downregulated genes, with >2 fold‑change and an adjusted P‑value <0.01 cut-offs. Functional annotations showed the DEGs were involved in immune system processes, including defence and general immune responses. This suggests a dysregulation of the immune system is strongly linked to the OS microenvironment, with DEGs potentially contributing to OS development and metastasis. Via GO based refinement, immune receptors CXCR4 and CD74 were found upregulated in OS[GS(1] (fold-change (3.38 and 4.35) and adjusted P-values (5.74E-26 and 7.8E-17), respectively). CXCR4 has been associated with other metastatic cancers, validating our approach. In summary, immune system dysregulation may contribute to OS development, with the upregulated immune receptors being potential druggable targets for novel drug delivery systems.