Periostin is associated with prognosis and immune cell infiltration in pancreatic adenocarcinoma based on integrated bioinformatics analysis

Abstract

Background:Pancreatic cancer is one of the most aggressive human malignancies.Previous research has shown that periostin (POSTN) promotes pancreatic cancer cellproliferation, migration, and invasion. Further, POSTN is involved in tumor microenvi-ronment remodeling during tumor progression. However, the relationship betweenPOSTN expression, immune cell infiltration, and the efficacy of immunotherapy inpancreatic cancer is unclear.Methods:We conducted a comprehensive evaluation of POSTN differential expres-sion, examining mRNA and protein levels. To gather data, we utilized various data-bases including gene expression profiling interactive analysis 2 (GEPIA2), geneexpression omnibus (GEO), and the human protein atlas (HPA). To investigate thecorrelation betweenPOSTNexpression and clinical characteristics, we analyzed datafrom the Kaplan–Meier plotter database and clinical data sourced from the cancergenome atlas (TCGA). Furthermore, we performed gene ontology (GO) analysis,Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and gene setenrichment analysis (GSEA). Additionally, we explored the relationship betweenPOSTNexpression and immune cell infiltration, as well as the immunophenoscore(IPS), by leveraging the cancer immunome atlas (TCIA) database. Lastly, we examinedthe tumor mutational burden (TMB) in pancreatic cancer in relation toPOSTNexpression.Results:When compared with healthy pancreatic tissues, pancreatic cancer tissuesdisplayed significantly higher levels of POSTN, which was indicative of a worse prog-nosis.POSTNexpression was closely associated with extracellular matrix (ECM) orga-nization, ECM-receptor interaction, and focal adhesion by GO, KEGG pathway, and GSEA analyses. Higher expression ofPOSTNwas associated with increased infiltra-tion of M2 macrophages. Additionally, increased IPS was linked to lowerPOSTNexpression. IPS scores for CTLA4, PD-1/PDL1, and CTLA4/PD-1/PDL1 immunecheckpoint inhibitors were also higher in thePOSTN-low expression group, suggest-ing that lower expression ofPOSTNis associated with a better outcome with check-point inhibitor treatment.Conclusion:POSTN is related to pancreatic cancer prognosis, and may influenceimmune cell infiltration. High expression ofPOSTNis predicted to correlate withlower sensitivity to immunotherapy with checkpoint inhibitors in pancreaticcancer.