The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration

Abstract

Osteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein–protein interaction (PPI) network of these DEGs. By focusing on the hub gene TYROBP in the top 1 cluster, a conserved TYROBP co-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies.

Higher TYROBP and lower SOX6 as predictive biomarkers for poor prognosis of clear cell renal cell carcinoma: A pilot study

“…This protein functions in signal transduction, bone modeling, brain myelination, and inflammation by binding to zeta chain-associated protein kinase 70 kDa (ZAP-70) and spleen tyrosine kinase. [ 11 ] TYROBP is a regulatory protein of various activated receptors in natural killer cells, which activates small colloidal cells to recognize and phagocytose glioma cells. [ 12 ] TYROBP can mediate natural killer (NK) cell activation with NK cell receptors such as KIR2DS2 and KLRD1/KLRC2 heterodimer and promote NK cell receptors KIR2DS1 and KIR2DS2 and KIR2DS4, and ensure its stability on the cell surface, enhance and maintain the cytotoxic effect of NK cells.…”

Deciphering the molecular and clinical characteristics of TREM2, HCST, and TYROBP in cancer immunity: A comprehensive pan-cancer study

“…MEG3 and SIP1 exert regulatory effects on various tumors via mechanisms involving tumor macrophage aggregation and polarization, immune infiltration, chemotherapy sensitivity, PTEN, CCL7 transcription, and p53 signaling pathways [ [36] , [37] , [38] , [39] , [40] ]. One study on the role of the SPI1-TYROBP-FCER1G network in osteosarcoma occurrence and prognosis and its relationship with immune infiltration integrated the GEO database [ 41 ]. However, the associations between MEG3 and TREM2, HCST, TYROBP, and between SIP1 and TREM2 and HCST have not yet been characterized.…”

SPI1 is a prognostic biomarker of immune infiltration and immunotherapy efficacy in clear cell renal cell carcinoma

“…SPI1 can be a prognostic marker and immunotherapeutic target for gastric cancer patients [ 35 ]. Li et al found that SPI1 is associated with immune infiltration during oncogenesis [ 13 ]. However, the role of SPI1 in ccRCC is unknown, and the relationship between SPI1 and immune infiltrates in ccRCC remains unclear.…”

“…Transcriptional activation of SPI1 can enhance the tumorigenic potential of cervical cancer cells through its effect on PARP9 [ 12 ]. Importantly, Li et al demonstrated that the transcription factor SPI1 can promote the expression of CD86, CCL4/CXCL10/CX3CL1, and MHC-II, thereby increasing immune infiltration [ 13 ]. However, the relationship between of SPI1 expression and immune cell infiltration in ccRCC remains unclear.…”