Meng Kexin, Zhao Zerui, Gao Yaqing, Wu Keliang, Liu Wei, Wang Xiaoqing, Zheng Yi, Zhao Wei, Wang Bei
Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medical and Health Key Laboratory of Abdominal Medical Imaging, Jinan, China.
Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
Front Mol Biosci. 2024 Sep 16;11:1469775. doi: 10.3389/fmolb.2024.1469775. eCollection 2024.
Wilms tumor (WT) is the most common type of malignant abdominal tumor in children; it exhibits a high degree of malignancy, grow rapidly, and is prone to metastasis. This study aimed to construct a prognosis model based on anoikis-related genes (ARGs) and epithelial-mesenchymal transition (EMT)-related genes (ERGs) for WT patients; we assessed the characteristics of the tumor microenvironment and treatment efficacy, as well as identifying potential therapeutic targets. To this end, we downloaded transcriptome sequencing data and clinical data for WT and normal renal cortices and used R to construct and validate the prognostic model based on ARGs and ERGs. Additionally, we performed clinical feature analysis, nomogram construction, mutation analysis, drug sensitivity analysis, Connectivity Map (cMAP) analysis, functional enrichment analysis, and immune infiltration analysis. Finally, we screened the hub gene using the STRING database and validated it via experiments. In this way, we constructed a model with good accuracy and robustness, which was composed of seven anoikis- and EMT-related genes. Paclitaxel and mesna were selected as potential chemotherapeutic drugs and adjuvant chemotherapeutic drugs for the WT high-risk group by using the Genomics of Drug Sensitivity in Cancer (GDSC) and cMAP compound libraries, respectively. We proved the existence of a strong correlation between invasive immune cells and prognostic genes and risk scores. Next, we selected NTRK2 as the hub gene, and experiments confirmed that its inhibition can significantly inhibit the proliferation and migration of tumor cells and promote late apoptosis. In summary, we screened out the potential biomarkers and chemotherapeutic drugs that can improve the prognosis of patients with WT.
肾母细胞瘤(WT)是儿童最常见的腹部恶性肿瘤类型;它具有高度恶性,生长迅速,且易于转移。本研究旨在基于失巢凋亡相关基因(ARGs)和上皮-间质转化(EMT)相关基因(ERGs)构建WT患者的预后模型;我们评估了肿瘤微环境的特征和治疗效果,并确定潜在的治疗靶点。为此,我们下载了WT和正常肾皮质的转录组测序数据及临床数据,并使用R语言基于ARGs和ERGs构建并验证了预后模型。此外,我们进行了临床特征分析、列线图构建、突变分析、药物敏感性分析、连接图谱(cMAP)分析、功能富集分析和免疫浸润分析。最后,我们使用STRING数据库筛选出核心基因并通过实验进行验证。通过这种方式,我们构建了一个由七个与失巢凋亡和EMT相关的基因组成的、具有良好准确性和稳健性的模型。通过使用癌症药物敏感性基因组学(GDSC)和cMAP化合物库,分别为WT高危组选择了紫杉醇和巯乙磺酸钠作为潜在的化疗药物和辅助化疗药物。我们证明了浸润性免疫细胞与预后基因和风险评分之间存在强相关性。接下来,我们选择NTRK2作为核心基因,实验证实抑制它可显著抑制肿瘤细胞的增殖和迁移并促进晚期凋亡。总之,我们筛选出了可改善WT患者预后的潜在生物标志物和化疗药物。