Clinical significance of secreted phosphoprotein-1 overexpression in cancers

Dysregulated SPP1 expression has been involved in the pathogenic progression of various tumors. However, more information is still necessary to understand the adverse effects of SPP1 in cancers.

A systematic assessment was performed to determine the expression features of SPP1 and its clinical implications in a wide range of human cancer types. SPP1 expression was determined by implementing transcriptomic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) projects. The prognostic value of SPP1 was assessed by Kaplan-Meier method. SPP1-related protein network was constructed using the STRING database and visualized by Cytoscape. Functional enrichment analysis was conducted through the DAVID resources. The correlation between SPP1 expression and immune infiltration was examined using TIMER and TISIDB platforms with multiple algorithms.

SPP1 expression is commonly upregulated in diverse human cancers. Increased SPP1 significantly contributes to cancer progression with worse clinical outcomes. SPP1 is positively correlated with the abundance of functionally immunosuppressive lymphocytes such as regulatory T cells (Treg), myeloid-derived suppressor cells (MDSCs), M2-polarized macrophages, and cancer-associated fibroblasts (CAFs), and also associated with the upregulation of immunosuppressors such as colony-stimulating factor 1 receptor (CSF1R) and hepatitis A virus cellular receptor 2 (HAVCR2).

Elevated SPP1 recruits progressively a range of cancer pathways and contributes to poorer clinical outcomes. This study provides an integrative proof that SPP1 serves as a progressive and prognostic biomarker and a potential therapeutic target for the majority of cancer types.