Screening and identification Hub genes associated with immune cell infiltration and critical biomarkers in osteosarcoma
Purpose Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS. Methods The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells. Result CD8 + T cells, activated memory CD4 + T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes CCL5 , CXCL9 , CXCL13 , and HTRA1 , exhibited positive correlation with the infiltration of both CD8 + T cells and CD4 + T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics. Conclusion CCL5 , CXCL9 , CXCL13, and HTRA1 were OS hub genes positively correlate with CD8 + T cell and CD4 + T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.
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