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

Background: Pancreatic cancer is one of the most aggressive human malignancies. Previous research has shown that periostin (POSTN) promotes pancreatic cancer cell proliferation, migration, and invasion. Further, POSTN is involved in tumor microenvironment remodeling during tumor progression. However, the relationship between POSTN expression, immune cell infiltration, and the efficacy of immunotherapy in pancreatic cancer is unclear.

Methods: We conducted a comprehensive evaluation of POSTN differential expression, examining mRNA and protein levels. To gather data, we utilized various databases including gene expression profiling interactive analysis 2 (GEPIA2), gene expression omnibus (GEO), and the human protein atlas (HPA). To investigate the correlation between POSTN expression and clinical characteristics, we analyzed data from the Kaplan-Meier plotter database and clinical data sourced from the cancer genome atlas (TCGA). Furthermore, we performed gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). Additionally, we explored the relationship between POSTN expression and immune cell infiltration, as well as the immunophenoscore (IPS), by leveraging the cancer immunome atlas (TCIA) database. Lastly, we examined the tumor mutational burden (TMB) in pancreatic cancer in relation to POSTN expression.

Results: When compared with healthy pancreatic tissues, pancreatic cancer tissues displayed significantly higher levels of POSTN, which was indicative of a worse prognosis. POSTN expression was closely associated with extracellular matrix (ECM) organization, ECM-receptor interaction, and focal adhesion by GO, KEGG pathway, and GSEA analyses. Higher expression of POSTN was associated with increased infiltration of M2 macrophages. Additionally, increased IPS was linked to lower POSTN expression. IPS scores for CTLA4, PD-1/PDL1, and CTLA4/PD-1/PDL1 immune checkpoint inhibitors were also higher in the POSTN-low expression group, suggesting that lower expression of POSTN is associated with a better outcome with checkpoint inhibitor treatment.

Conclusion: POSTN is related to pancreatic cancer prognosis, and may influence immune cell infiltration. High expression of POSTN is predicted to correlate with lower sensitivity to immunotherapy with checkpoint inhibitors in pancreatic cancer.