Secreted phosphoprotein 1 as a potential prognostic and immunotherapy biomarker in multiple human cancers

Abstract

Secreted phosphoprotein 1 (<i>SPP1</i>) is involved in immune regulation, cell survival, and tumor progression. Studies have demonstrated that <i>SPP1</i> plays an important role in certain individual tumors. However, the expression profile and oncogenic features of <i>SPP1</i> in diverse cancers are remaining unknown. Therefore, we performed a comprehensive analysis using The Cancer Genome Atlas (TCGA) database. Raw data of 33 cancer types were download from the University of California Santa Cruz (UCSC) Xena website. The expression of <i>SPP1</i> and its relationship with tumor prognosis, immune invasion, tumor microenvironment, and immunotherapy were analyzed using the R language. The function analysis was conducted using Gene Set Enrichment Analysis (GSEA). The oncogenic features of <i>SPP1</i> was validated by wound-healing assay and EdU staining assay. <i>SPP1</i> highly expressed in most cancers. The expression of <i>SPP1</i> was significant related to prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes, suggested that <i>SPP1</i> plays an essential role in the tumor immune microenvironment and immune cell infiltration. The immune/stromal scores correlated positively with the <i>SPP1</i> expression, and the relationship was affected by tumor heterogeneity and immunotherapy. In addition, <i>SPP1</i> could predict the response of tumor immunotherapy. Functional analysis revealed the <i>SPP1</i>-associated terms and pathways. Finally, <i>SPP1</i> significantly elevated cell proliferation and migration in A549, Huh7, HT-29, A2780 tumor cell lines. In conclusion, this study indicated that <i>SPP1</i> involved in tumorigenesis, tumor progression, and regulated tumor immune microenvironment, revealing <i>SPP1</i> might be a potential target for evaluating prognosis and immunotherapy in multiple cancers.