Ding Chen, Gao Hongjie, Zhang Liting, Lu Zhiyi, Zhang Bowen, Li Ding, Sun Fengyin
Department of Pediatric Surgery, Qilu Hospital of Shandong University, 107 Wenhua West Road, Jinan, 250012, China.
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.
Sci Rep. 2025 Apr 4;15(1):11639. doi: 10.1038/s41598-025-96094-4.
Wilms tumor (WT) is a common renal malignancy in pediatric patients. Interleukin (receptors) (IL(R)s) play significant roles in tumor biology, however, their specific involvement in WT remains inadequately understood. We employed univariate Cox regression analysis to screen for certain IL(R) genes associated with prognosis and then analyzed their expression patterns. A prognostic model was constructed based on five selected IL(R)s using the LASSO Cox regression algorithm. To further elucidate the relationship between the prognostic model and the immune microenvironment, we conducted immune-related analyses. Additionally, we performed experiments to verify the roles of IL20RA and IL19 in WT. Finally, CNV, methylation and pan-cancer analysis were performed for IL19 and IL20RA. Our analysis ultimately identified five genes associated with prognosis: IL20RA, IL19, IL24, IL11 and IL17RD. The prognostic model incorporating these five genes demonstrated robust predictive power in both training and validation cohorts. Notably, IL19 and IL20RA were found to promote epithelial-mesenchymal transition (EMT) through the STAT3/SNAIL pathway, thereby contributing to tumor progression. Furthermore, significant differences in immune function and checkpoint expression were observed between the two groups. The high-risk group exhibiting a lower TIDE score, which suggests a potentially better response to immunotherapy. This study introduces a novel IL(R)-based prognostic signature for WT, highlighting IL20RA as a potential therapeutic target. These findings offer valuable insights for future studies on WT.
肾母细胞瘤(WT)是儿科患者中常见的肾脏恶性肿瘤。白细胞介素(受体)(IL(R)s)在肿瘤生物学中发挥着重要作用,然而,它们在WT中的具体作用仍未得到充分了解。我们采用单变量Cox回归分析筛选与预后相关的某些IL(R)基因,然后分析它们的表达模式。使用LASSO Cox回归算法基于五个选定的IL(R)s构建了一个预后模型。为了进一步阐明预后模型与免疫微环境之间的关系,我们进行了免疫相关分析。此外,我们进行了实验以验证IL20RA和IL19在WT中的作用。最后,对IL19和IL20RA进行了拷贝数变异(CNV)、甲基化和泛癌分析。我们的分析最终确定了五个与预后相关的基因:IL20RA、IL19、IL24、IL11和IL17RD。包含这五个基因的预后模型在训练和验证队列中均显示出强大的预测能力。值得注意的是,发现IL19和IL20RA通过STAT3/SNAIL途径促进上皮-间质转化(EMT),从而促进肿瘤进展。此外,两组之间在免疫功能和检查点表达方面观察到显著差异。高危组的肿瘤免疫功能障碍和排除(TIDE)评分较低,这表明对免疫治疗可能有更好的反应。本研究为WT引入了一种基于IL(R)的新型预后特征,突出了IL20RA作为潜在治疗靶点。这些发现为WT的未来研究提供了有价值的见解。