• Liwen Fan, Xinyu Wang, Qing Chang, Yue Wang, Wenjie Yang, and Linlin Liu.
• Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.
• Medicine (Baltimore). 2022 Oct 21; 101 (42): e30966e30966.

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and incurable cancer with a dismal prognosis. In this study, we aimed to explore potential predictors for the prognosis and immunological characteristics of PDAC. Estimation of stromal and immune cells in malignant tumors, using expression data (ESTIMATE) method was applied to calculate the immune and stromal scores of 206 PDAC samples from GSE71729. R package of "limma" was utilized to identify differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted for functional exploration. Protein-protein interaction (PPI) network and Univariate Cox analysis were conducted to select key prognostic genes of PDAC. Gene set enrichment analysis (GSEA) was applied to investigate the roles of IL2RA in PDAC. Single sample GSEA (ssGSEA) was performed to evaluate the immunological characteristics of PDAC samples. Wilcoxon rank sum test was conducted to compare the difference of immunological characteristics of PDAC samples between low IL2RA and high IL2RA. Spearman correlation analysis was used to explore the correlations of IL2RA expression and immune checkpoint genes. A total of 747 DEGs were identified between low and high immune/stromal groups. Functional exploration revealed upregulated DEGs were associated with immune-related activities, whereas downregulated DEGs were involved in inflammatory-related activities. IL2RA was selected as the critical gene by overlapping the hub genes in PPI network and prognostic genes. Significantly, IL2RA expression was significantly elevated in PDAC and patients with higher IL2RA expression had worse prognoses. The immunological and oncogenic roles of IL2RA in PDAC were evidenced by GSEA. Furthermore, PDAC samples with high IL2RA expression exhibited increased immune infiltration and better immunotherapy responses. IL2RA expression was positively correlated with PDCD1, CD274, CTLA4, IDO1, TDO2, and TIGT. Higher expression of IL2RA predicts worse survival outcomes and increased immune infiltration in PDAC. PDAC patients with high IL2RA expression might potentially benefit from immunotherapy.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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