Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.
Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
Medicine (Baltimore). 2022 Oct 21;101(42):e30966. doi: 10.1097/MD.0000000000030966.
Pancreatic 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.
胰腺导管腺癌（PDAC）是一种高度侵袭性和无法治愈的癌症，预后极差。在这项研究中，我们旨在探讨 PDAC 预后和免疫特征的潜在预测因子。使用表达数据（ESTIMATE）方法估计肿瘤中的基质和免疫细胞，以计算来自 GSE71729 的 206 个 PDAC 样本的免疫和基质评分。使用“limma”R 包识别差异表达基因（DEGs）。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析以进行功能探索。进行蛋白质-蛋白质相互作用（PPI）网络和单变量 Cox 分析以选择 PDAC 的关键预后基因。进行基因集富集分析（GSEA）以研究 IL2RA 在 PDAC 中的作用。进行单样本 GSEA（ssGSEA）以评估 PDAC 样本的免疫学特征。使用 Wilcoxon 秩和检验比较低 IL2RA 和高 IL2RA 组 PDAC 样本的免疫学特征差异。使用 Spearman 相关分析探讨 IL2RA 表达与免疫检查点基因的相关性。在低免疫/基质组和高免疫/基质组之间鉴定出 747 个 DEGs。功能探索表明上调的 DEGs 与免疫相关活性有关，而下调的 DEGs 则与炎症相关活性有关。通过重叠 PPI 网络和预后基因中的枢纽基因，选择 IL2RA 作为关键基因。重要的是，在 PDAC 中 IL2RA 的表达显著升高，并且具有更高 IL2RA 表达的患者预后更差。GSEA 证实了 IL2RA 在 PDAC 中的免疫和致癌作用。此外，具有高 IL2RA 表达的 PDAC 样本表现出增加的免疫浸润和更好的免疫治疗反应。IL2RA 表达与 PDCD1、CD274、CTLA4、IDO1、TDO2 和 TIGT 呈正相关。IL2RA 表达较高预示着 PDAC 患者的生存结局较差且免疫浸润增加。高 IL2RA 表达的 PDAC 患者可能从免疫治疗中受益。
