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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1469775

The Synergistic Effects of Anoikis-Related Genes and EMT-Related Genes in the Prognostic Prediction of Wilms Tumor

Provisionally accepted
Kexin Meng Kexin Meng 1Zerui Zhao Zerui Zhao 2Yaqing Gao Yaqing Gao 1*Keliang Wu Keliang Wu 2*Wei Liu Wei Liu 3*Xiaoqing Wang Xiaoqing Wang 3Yi Zheng Yi Zheng 2Wei Zhao Wei Zhao 2,4*Bei Wang Bei Wang 1*
  • 1 Department of Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China
  • 2 Shandong University, Jinan, China
  • 3 Department of Pediatric Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong Province, China
  • 4 Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China

The final, formatted version of the article will be published soon.

    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 in vitro 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.

    Keywords: Wilms Tumor, Anoikis, EMT, Prognostic model, Tumor Microenvironment

    Received: 24 Jul 2024; Accepted: 03 Sep 2024.

    Copyright: © 2024 Meng, Zhao, Gao, Wu, Liu, Wang, Zheng, Zhao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yaqing Gao, Department of Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, Shandong Province, China
    Keliang Wu, Shandong University, Jinan, China
    Wei Liu, Department of Pediatric Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong Province, China
    Wei Zhao, Shandong University, Jinan, China
    Bei Wang, Department of Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, Shandong Province, China

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