Wang Pengpeng, Gao Xiang, Zheng Weijie, Zhang Junnan
Police-Dog Technology Department, Criminal Investigation Police University of China, Shenyang 110034, China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
J Proteomics. 2024 Sep 30;308:105277. doi: 10.1016/j.jprot.2024.105277. Epub 2024 Aug 8.
Pancreatic adenocarcinoma (PAAD) is a prevalent and highly malignant gastrointestinal tumor. Therefore, exploring the mechanisms of drug resistance and immune pathways in PAAD is crucial for clinical treatment. In this study, a total of 497 differentially expressed genes (DEGs) were identified between normal and PAAD samples, and which were enriched to 117 GO terms and 7 functional pathways. Subsequently, 5 overall survival-related DEGs (ESRP1, KRT6A, H2BC11, H2BC4 and KLK) was generated using Cox hazards regression analysis in TCGA dataset. Furthermore, the weighted gene co-expression network analysis revealed a strong association between ESRP1 and PAAD among 5 survival-related DEGs. Patients were divided into two clusters based on ESRP1 expression levels, and low ESRP1 expression existed stronger immune infiltration and higher expression of immunomodulatory targets than high ESRP1 expression by single-sample gene set enrichment analysis, which indicated that low ESRP1 expression was associated with longer survival compared to high ESRP1 expression. Finally, our study also found that immune cells distribution and immunomodulatory targets gene expression in the GEO dataset were similar to the TCGA cohort. Overall, our findings suggest that ESRP1 may play a role in influencing immune contexture and regulating immune function of PAAD patients by integrating data from various databases. SIGNIFICANCE: Utilizing TCGA and GEO datasets, this study uncovers the significant impact of epithelial splicing regulatory protein 1 (ESRP1) on PAAD. ESRP1 emerges as a key regulator of immune function, influencing tumor microenvironment and immune cell infiltration. Cluster analysis shows that low ESRP1 expression correlates with enhanced immune activity, predicting better prognosis. This discovery suggests that ESRP1 can serve as a potential biomarker for the prognosis of PAAD, offering new insights into personalized immunotherapy by influencing immune regulation and tumor progression.
胰腺腺癌（PAAD）是一种常见且高度恶性的胃肠道肿瘤。因此，探索PAAD中的耐药机制和免疫途径对临床治疗至关重要。在本研究中，共鉴定出正常样本与PAAD样本之间的497个差异表达基因（DEG），这些基因富集到117个基因本体（GO）术语和7条功能途径。随后，在TCGA数据集中使用Cox风险回归分析生成了5个与总生存相关的DEG（ESRP1、KRT6A、H2BC11、H2BC4和KLK）。此外，加权基因共表达网络分析显示，在5个与生存相关的DEG中，ESRP1与PAAD之间存在强关联。根据ESRP1表达水平将患者分为两个聚类，通过单样本基因集富集分析发现，与高ESRP1表达相比，低ESRP1表达存在更强的免疫浸润和更高的免疫调节靶点表达，这表明低ESRP1表达与较长生存期相关。最后，我们的研究还发现GEO数据集中的免疫细胞分布和免疫调节靶点基因表达与TCGA队列相似。总体而言，我们的研究结果表明，ESRP1可能通过整合来自各种数据库的数据，在影响PAAD患者的免疫背景和调节免疫功能中发挥作用。意义：本研究利用TCGA和GEO数据集，揭示了上皮剪接调节蛋白1（ESRP1）对PAAD的重大影响。ESRP1成为免疫功能的关键调节因子，影响肿瘤微环境和免疫细胞浸润。聚类分析表明，低ESRP1表达与增强的免疫活性相关，预示着更好的预后。这一发现表明，ESRP1可作为PAAD预后的潜在生物标志物，通过影响免疫调节和肿瘤进展为个性化免疫治疗提供新的见解。
