Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, P.R. China.
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, P.R. China.
Anticancer Res. 2024 Sep;44(9):3829-3842. doi: 10.21873/anticanres.17209.
BACKGROUND/AIM: Autophagy and immunity play important roles in the growth of malignant tumors and are promising targets for tumor therapy. This study was conducted to identify differentially expressed immune genes related to autophagy in Wilms' tumor (WT) and analyze their correlation with the disease prognosis.
The public data of WT and normal kidney tissues were downloaded from TCGA, ImmPort, and GeneCards databases to obtain differentially expressed immune genes associated with autophagy. Survival analysis, ROC curve, and clinical relevance filtering were used to screen the key gene plasminogen activator urokinase (PLAU). The univariable and multivariable Cox regression model analyses were used to analyze the prognostic factors of overall survival (OS) in patients with WT. Then, GO enrichment, KEGG pathway analysis and GSEA were used to enrich and analyze differentially expressed genes. The relationship between PLAU gene expression and tumor microenvironment and infiltration of immune cells was analyzed, as well as between the expression of PLAU and epigenetic modifications.
PLAU gene expression was associated with survival and prognosis in WT patients and was an independent prognostic indicator of OS in patients. The GO, KEGG, and GSEA analysis results suggested that PLAU may be involved in RNA transcription and epithelial cell migration. High expression of PLAU was also associated with increased immune cell infiltration and a higher presence of antitumor immune cells. The low expression of PLAU in WT was related to DNA methylation and may be also co-regulated by miR-342-3p.
PLAU can be used as an independent prognostic biomarker for WT. Low expression of PLAU is associated with poor prognosis in WT patients. Evidence on the prognostic value of PLAU gene and the pathways that may be associated with its expression is invaluable for the development of new therapies for WT.
背景/目的:自噬和免疫在恶性肿瘤的生长中发挥着重要作用,是肿瘤治疗的有前途的靶点。本研究旨在鉴定与 Wilms 瘤(WT)中自噬相关的差异表达免疫基因,并分析其与疾病预后的相关性。
从 TCGA、ImmPort 和 GeneCards 数据库下载 WT 和正常肾脏组织的公共数据,以获得与自噬相关的差异表达免疫基因。采用生存分析、ROC 曲线和临床相关性筛选方法筛选关键基因尿激酶型纤溶酶原激活物(PLAU)。采用单变量和多变量 Cox 回归模型分析 WT 患者总生存期(OS)的预后因素。然后,进行 GO 富集、KEGG 通路分析和 GSEA 分析,以富集和分析差异表达基因。分析 PLAU 基因表达与肿瘤微环境和免疫细胞浸润的关系,以及 PLAU 表达与表观遗传修饰的关系。
PLAU 基因表达与 WT 患者的生存和预后相关,是 WT 患者 OS 的独立预后指标。GO、KEGG 和 GSEA 分析结果表明,PLAU 可能参与 RNA 转录和上皮细胞迁移。PLAU 高表达与免疫细胞浸润增加和抗肿瘤免疫细胞增多有关。WT 中 PLAU 的低表达与 DNA 甲基化有关,也可能与 miR-342-3p 共同调控。
PLAU 可作为 WT 的独立预后生物标志物。WT 患者中 PLAU 低表达与预后不良相关。PLAU 基因预后价值的证据及其可能与其表达相关的途径对开发 WT 的新疗法具有重要意义。