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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1433008
This article is part of the Research Topic Perspectives on Omics Analysis in Solid Tumors: Advancing Cancer Research View all 7 articles

CRISPR-Cas9 Screening Develops an Epigenetic and Transcriptional Gene Signature for Risk Stratification and Target Prediction in Neuroblastoma

Provisionally accepted
Liaoran Zhang Liaoran Zhang 1Jialin Mo Jialin Mo 2*Hao Shi Hao Shi 1Jing Xiong Jing Xiong 1*Yeerfan Aierken Yeerfan Aierken 1*Feng Chen Feng Chen 1*Yujie Tang Yujie Tang 2*Kewen Zhao Kewen Zhao 3*Zhibao Lv Zhibao Lv 1*Kezhe Tan Kezhe Tan 1*
  • 1 School of Medicine, Shanghai Jiao Tong University, Department of General Surgery, Shanghai Children's Hospital, Shanghai, China
  • 2 Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
  • 3 State Key Laboratory of Oncogenes and Related Genes, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China

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

    Objectives: Neuroblastoma (NB), a pediatric malignancy of the peripheral nervous system, is characterized by epigenetic and transcriptional (EP-TF) anomalies. This study aimed to develop an EP-TF clinical prognostic model for NB using CRISPR-Cas9 knockout screening. Results: An integrative analysis was conducted using CRISPR-Cas9 screening in vitro and in vivo with public NB datasets to identify 35 EP-TF genes that exhibited the highest expression in NB and were highly dependent on cancer viability. After univariate analysis, 27 of these 35 genes were included in the least absolute shrinkage and selection operator screen. We established and biologically validated a prognostic EP-TF model encompassing RUVBL1, LARP7, GTF3C4, THAP10, SUPT16H, TIGD1, SUV39H2, TAF1A, SMAD9 and FEM1B across diverse NB cohorts. MYCN serves a potential upstream regulator of EP-TF genes. The high-risk subtype exhibited traits associated with the malignant cell cycle, MYCN-linked signaling and chromatin remodeling, all of which are correlated with poor prognosis and immunosuppression. MEK inhibitors have emerged as promising therapeutic agents for targeting most EP-TF risk genes in NB. Conclusions: Our novel prognostic model shows significant potential for predicting and evaluating the overall survival of NB patients, offering insights into therapeutic targets. Keywords: neuroblastoma, epigenetic and transcriptional genes, prognostic model, MYCN, drug targets.

    Keywords: Neuroblastoma, epigenetic and transcriptional genes, Prognostic model, MYCN, Drug Targets

    Received: 15 May 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Zhang, Mo, Shi, Xiong, Aierken, Chen, Tang, Zhao, Lv and Tan. 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:
    Jialin Mo, Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Shanghai Municipality, China
    Jing Xiong, School of Medicine, Shanghai Jiao Tong University, Department of General Surgery, Shanghai Children's Hospital, Shanghai, 200062, China
    Yeerfan Aierken, School of Medicine, Shanghai Jiao Tong University, Department of General Surgery, Shanghai Children's Hospital, Shanghai, 200062, China
    Feng Chen, School of Medicine, Shanghai Jiao Tong University, Department of General Surgery, Shanghai Children's Hospital, Shanghai, 200062, China
    Yujie Tang, Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Shanghai Municipality, China
    Kewen Zhao, State Key Laboratory of Oncogenes and Related Genes, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Shanghai Municipality, China
    Zhibao Lv, School of Medicine, Shanghai Jiao Tong University, Department of General Surgery, Shanghai Children's Hospital, Shanghai, 200062, China
    Kezhe Tan, School of Medicine, Shanghai Jiao Tong University, Department of General Surgery, Shanghai Children's Hospital, Shanghai, 200062, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.