AUTHOR=Zhao Kaidi , Ma Zhou , Zhang Wei 

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

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.732822

DOI=10.3389/fgene.2021.732822

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold><italic>SPP1</italic>, secreted phosphoprotein 1, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. Previous studies have proven <italic>SPP1</italic> 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 <italic>SPP1</italic> in cervical cancer.</p><p><bold>Methods:</bold> We aimed to demonstrate the relationship between <italic>SPP1</italic> expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated <italic>SPP1</italic> 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 <italic>SPP1</italic> 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 <italic>SPP1</italic>-binding protein network was built by the STRING tool. Enrichment analysis by the R package clusterProfiler was used to explore potential function of <italic>SPP1</italic>. 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 <italic>SPP1</italic> expression in cervical cancer.</p><p><bold>Results:</bold> Pan-cancer data analysis showed that <italic>SPP1</italic> 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 <italic>SPP1</italic> could be a potential diagnostic biomarker (AUC = 0.877). High <italic>SPP1</italic> expression was associated with poorer overall survival (OS) (<italic>P</italic> = 0.032). Further enrichment and immune infiltration analysis revealed that high <italic>SPP1</italic> expression was correlated with regulating the infiltration level of neutrophil cells and some immune cell types, including macrophage and DC.</p><p><bold>Conclusion:</bold><italic>SPP1</italic> 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, <italic>SPP1</italic> may become a promising prognostic biomarker for cervical cancer patients.</p>