A pan-cancer analysis of the oncogenic role of secreted phosphoprotein 1 (SPP1) in human cancers

BACKGROUND: Emerging evidence suggests that secreted phosphoprotein 1 (SPP1) is involved in tumor cell progression in multiple cancer types. However, the role of SPP1 in different cancers is still not clear. METHODS: We used data from The Cancer Genome Atlas (TCGA) to analyze the multiomic roles of SPP1, including RNA expression, DNA methylation, protein phosphorylation, immune infiltration, and overall survival (OS) in 33 tumor types. RESULTS: SPP1 is highly expressed in most cancer types, and its methylation variability and mRNA expression level are both correlated with prognosis in multiple cancer types. A higher S234 phosphorylation level was observed in 4 types of tumors, including colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD). SPP1 expression level was positively associated with the infiltration level of dendritic cells, neutrophils, and macrophages in multiple cancer types. It was also significantly positively correlated with hepatitis A virus cellular receptor 2 (HAVCR2), which was observed in most tumor types, including brain lower grade glioma (LGG) and ovarian serous cystadenocarcinoma (OV). Moreover, myeloid cell differentiation and leukocyte migration were observed in the enrichment analysis, suggesting that SPP1 might induce immune escape. CONCLUSIONS: Pan-cancer analysis using a multiomic approach offered a comprehensive overview of SPP1. This protein plays an important role in most of the analyzed tumor types and could be a valuable prognostic marker across different types of cancer.