Comprehensive Analysis to Identify SPP1 as a Prognostic Biomarker in Cervical Cancer

Abstract

<b>Background:</b> <i>SPP1</i>, secreted phosphoprotein 1, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. Previous studies have proven <i>SPP1</i> overexpressed in a variety of cancers and can be identified as a prognostic factor, while no study has explored the function and carcinogenic mechanism of <i>SPP1</i> in cervical cancer. <b>Methods:</b> We aimed to demonstrate the relationship between <i>SPP1</i> expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated <i>SPP1</i> expression of cervical cancer in the Gene Expression Omnibus (GEO) database, including GSE7803, GSE63514, and GSE9750. The receiver operating characteristic (ROC) curve was used to evaluate the feasibility of <i>SPP1</i> as a differentiating factor by the area under curve (AUC) score. Cox regression and logistic regression were performed to evaluate factors associated with prognosis. The <i>SPP1</i>-binding protein network was built by the STRING tool. Enrichment analysis by the R package clusterProfiler was used to explore potential function of <i>SPP1</i>. The single-sample GSEA (ssGSEA) method from the R package GSVA and TIMER database were used to investigate the association between the immune infiltration level and <i>SPP1</i> expression in cervical cancer. <b>Results:</b> Pan-cancer data analysis showed that <i>SPP1</i> expression was higher in most cancer types, including cervical cancer, and we got the same result in the GEO database. The ROC curve suggested that <i>SPP1</i> could be a potential diagnostic biomarker (AUC = 0.877). High <i>SPP1</i> expression was associated with poorer overall survival (OS) (<i>P</i> = 0.032). Further enrichment and immune infiltration analysis revealed that high <i>SPP1</i> expression was correlated with regulating the infiltration level of neutrophil cells and some immune cell types, including macrophage and DC. <b>Conclusion:</b> <i>SPP1</i> expression was higher in cervical cancer tissues than in normal cervical epithelial tissues. It was significantly associated with poor prognosis and immune cell infiltration. Thus, <i>SPP1</i> may become a promising prognostic biomarker for cervical cancer patients.