C-C Motif Chemokine Ligand 5 (CCL5): A Potential Biomarker and Immunotherapy Target for Osteosarcoma.

Abstract

Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue, which has an insidious onset and is difficult to detect early, and few early diagnostic markers with high specificity and sensitivity. Therefore, this study aims to identify potential biomarkers that can help diagnose OS in its early stages and improve the prognosis of patients. The data sets of GSE12789, GSE28424, GSE33382 and GSE36001 were combined and normalized to identify Differentially Expressed Genes (DEGs). The data were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) and Disease Ontology (DO). The hub gene was selected based on the common DEG that was obtained by applying two regression methods: the Least Absolute Shrinkage and Selection Operator (LASSO) and Support vVector Machine (SVM). Then the diagnostic value of the hub gene was evaluated in the GSE42572 data set. Finally, the correlation between immunocyte infiltration and key genes was analyzed by CIBERSORT. The regression analysis results of LASSO and SVM are the following three DEGs: FK501 binding protein 51 (FKBP5), C-C motif chemokine ligand 5 (CCL5), complement component 1 Q subcomponent B chain (C1QB). We evaluated the diagnostic performance of three biomarkers (FKBP5, CCL5 and C1QB) for osteosarcoma using receiver operating characteristic (ROC) analysis. In the training group, the area under the curve (AUC) of FKBP5, CCL5 and C1QB was 0.907, 0.874 and 0.676, respectively. In the validation group, the AUC of FKBP5, CCL5 and C1QB was 0.618, 0.932 and 0.895, respectively. It is noteworthy that these genes were more expressed in tumor tissues than in normal tissues by various immune cell types, such as plasma cells, CD8+ T cells, T regulatory cells (Tregs), activated NK cells, activated dendritic cells and activated mast cells. These immune cell types are also associated with the expression levels of the three diagnostic genes that we identified. We found that CCL5 can be considered an early diagnostic gene of osteosarcoma, and CCL5 interacts with immune cells to influence tumor occurrence and development. These findings have important implications for the early detection of osteosarcoma and the identification of novel therapeutic targets.