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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- 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
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
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