PPAR-δ as a prognostic biomarker and its association with immune infiltrates in breast cancer PPAR-δ as a prognostic biomarker and its association with immune infiltrates in breast cancer.

Abstract

While peroxisome proliferator-activated receptor δ (PPAR-δ) and its associated signaling pathways have been shown to play an important regulatory role in various malignant tumors, in breast cancer, its potential influence on immune infiltration and its ability to serve as a prognostic marker remains unclear. BRCA patient samples with matched paracancerous samples were obtained from The Cancer Genome Atlas (TCGA). PPAR-δ expression, its potential effect on immune cell infiltration and its association to clinicopathological features were examined. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Single-Sample Gene Set Enrichment Analysis (ssGSEA) were utilized for functional and pathway enrichment and to quantify the extent of immune cell infiltration. Kaplan-Meier analysis and Cox regression analysis (nomogram) were performed to assess the association between PPAR- δ and predicted survival. To confirm these findings, an allograft tumor mouse model was generated and treated with a PPAR-δ inhibitor to examine the role of PPAR-δ expression in vivo; while immunohistochemistry (IHC) was performed to examine PPAR-δ expression in paired BRCA patient samples in vitro. Overall, the findings presented herein suggest that PPAR-δ plays a crucial role in breast cancer progression and prognosis and may serve as a survival predictive biomarker.