Research On The Expression,Prognosis And Immune Infiltration Of SPP1 In Colorectal Cancer Based On Bioinformatics

Background and Objective: Secretory phosphoprotein 1(SPP1),also known as Osteopontin,is a member of the small integrin-binding ligand n-linked glycoprotein family.Many studies have demonstrated that SPP1 is over expressed in a variety of cancers and can be identified as a prognostic factor.However,lacking of SPP1 in survival prognosis and immune infiltration of CRC patients,the purpose of this study was to investigate SPP1’s expression,prognostic value,immune infiltration,potential function and its mechanism in CRC based on bioinformatics analysis.Methods: First,the expression levels of SPP1 in CRC and various cancers were analyzed using the GEPIA database.The Wilcoxon rank sum test was used to compare SPP1 expression levels in normal colorectal tissues and CRC tissues.The HPA database provides SPP1 protein expression data in normal colorectal tissues and CRC.The ROC was used to assess whether SPP1 had good predictive power.Logistic regression analysis and Wilcoxon rank sum test were used to assess the association between SPP1 expression and clinical characteristics.The prognostic value of SPP1 was ultimately determined by survival analysis using the Kaplan-meier method and the Progno Scan database,as well as by Cox multivariable regression analysis using relevant modules from the TIMER database.The R-package Clusterprofiler enrichment analysis was used to explore the signaling pathways and potential biological functions involved in SPP1.Correlations between SPP1 and immune-infiltrating cells were assessed by using ss GSEA and TIMER database.In addition,we further analyzed the correlation between SPP1 expression and gene markers of immune-infiltrating cells by using the TIMER database and the GEPIA database.Results: Analysis of the relationship between SPP1 expression and pan-cancer showed that SPP1 was highly expressed in most cancers,including CRC.At the same time,the expression level of SPP1 protein in CRC tissues was also higher than that in normal colorectal tissues.The area under the curve of the ROC curve(AUC = 0.846)showed that SPP1 had a high accuracy in predicting the prognosis of CRC.In CRC,the expression of SPP1 is closely related to tumor stage and DSS.SPP1 overexpression led to a significant decrease in OS,DSS,and DFS survival in CRC patients.SPP1 could be defined as an independent prognostic biomarker for CRC by multivariable Cox regression analysis(HR = 1.459;95% CI: 1.030-2.067;P = 0.033).Go,KEGG and GSEA analysis showed that SPP1 was involved in many signaling pathways or activities related to cellular metabolism,metastasis,immune escape and carcinogenesis.SPP1 expression was positively correlated with the infiltration of macrophages,dendritic cell,neutrophil and CD8 + T cells in CRC.Analysis of TIMER and GEPIA databases showed that SPP1 expression was strongly correlated with immune gene markers such as TAMs,DC,T cell exhaustion and Treg.Conclusion: High expression of SPP1 in CRC may be used as a prognostic biomarker and closely related to its immune infiltration.Overexpression of SPP1 increased the infiltration of macrophages,dendritic cell,neutrophil and CD8 + T cells,and positively correlated with the gene markers of immune infiltration,and all these may provide a new research direction for optimizing the efficacy of anti-colorectal cancer immunotherapy.