2. Academic Validation
  3. Comprehensive analysis identifies ubiquitin ligase FBXO42 as a tumor-promoting factor in neuroblastoma

Comprehensive analysis identifies ubiquitin ligase FBXO42 as a tumor-promoting factor in neuroblastoma

  • Sci Rep. 2024 Aug 12;14(1):18697. doi: 10.1038/s41598-024-69760-2.
Jianwu Zhou 1,  Qijun Li 2,  Xiaobin Deng 1,  Liang Peng 1,  Jian Sun 1,  Yao Zhang 1,  Yifei Du 3
Affiliations

Affiliations

  • 1 Department of Pediatric Surgical Oncology, Children's Hospital of Chongqing Medical University; and the National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China.
  • 2 Laboratory Animal Center, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
  • 3 Department of Pediatric Surgical Oncology, Children's Hospital of Chongqing Medical University; and the National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. doephy@163.com.
PMID: 39134694 DOI: 10.1038/s41598-024-69760-2
Abstract

Neuroblastoma, the deadliest solid tumor in children, exhibits alarming mortality rates, particularly among high-risk cases. To enhance survival rates, a more precise risk stratification for patients is imperative. Utilizing proteomic data from 34 cases with or without N-Myc amplification, we identified 28 differentially expressed ubiquitination-related proteins (URGs). From these, a prognostic signature comprising 6 URGs was constructed. A nomogram incorporating clinical-pathological parameters yielded impressive AUC values of 0.88, 0.93, and 0.95 at 1, 3, and 5 years, respectively. Functional experiments targeting the E3 ubiquitin Ligase FBXO42, a component of the prognostic signature, revealed its TP53-dependent promotion of neuroblastoma cell proliferation. In conclusion, our ubiquitination-related prognostic model robustly predicts patient outcomes, guiding clinical decisions. Additionally, the newfound pro-proliferative role of FBXO42 offers a novel foundation for understanding the molecular mechanisms of neuroblastoma.

Keywords

Bioinformatics; FBXO42; Neuroblastoma; Proliferation; TP53.

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