Identification of the Genetic Association Between Ferroptosis and immune in Pancreatic Cancer

Abstract

The morbidity and mortality rates of pancreatic cancer are increasing annually. Immunotherapy for pancreatic cancer has not yielded good results, and immunosuppression is now thought to be the key factor. Ferroptosis plays an important role in pancreatic cancer. However, the mechanism of ferroptosis in pancreatic cancer immunosuppression remains unclear. To investigate the relationship between Ferroptosis and immunosuppression in pancreatic cancer.We analyzed differentially expressed genes in the center of pancreatic cancer and pancreatic ductal adenocarcinoma (PDAC) tissues using bioinformatics techniques in the Gene Expression Omnibus and found genes associated with Ferroptosis in the FerrDb database. We then performed enrichment and protein–protein interaction (PPI) network analyses to explore DEG-enriched functions and pathways. Additionally, hub gene expression was explored using the STRING database. The TISIDB database was used to analyze correlations among key genes and immune characteristics. Finally, the expression of the key genes was confirmed in vitro. DEGs were first screened from the gene expression profiles of the GSE16515 and TCGA datasets. Simultaneously, the genes associated with ferroptosis intersected. Then, 39 common genes were identified in the three datasets. Functional analysis revealed that common DEGs were mostly related to lipid metabolism and ROS signaling pathways. Among the top 20 hub genes, CA9 was the most significant potential biomarker of PC. CA9 expression strongly correlates with chemokines, chemokine receptors, and immunomodulators. Finally, RT-qPCR was conducted to demonstrate CA9 expression in PC cell lines. Knockdown of CA9 can significantly reduce chemokines expression. We identified 20 hub genes that significantly affects the association between ferroptosis and PC. CA9 maybe a key player in pancreatic cancer immunosuppression and has potential treatment value for PC.