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综合分析鉴定泛素连接酶 FBXO42 为神经母细胞瘤中的肿瘤促进因子。

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

机构信息

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.

Laboratory Animal Center, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

出版信息

Sci Rep. 2024 Aug 12;14(1):18697. doi: 10.1038/s41598-024-69760-2.

DOI:10.1038/s41598-024-69760-2
PMID:39134694
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11319589/
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.

摘要

神经母细胞瘤是儿童中最致命的实体肿瘤，死亡率令人震惊，尤其是高危病例。为了提高生存率，对患者进行更精确的风险分层至关重要。利用来自 34 例有或无 N-Myc 扩增的蛋白质组学数据，我们鉴定出 28 种差异表达的泛素化相关蛋白（URGs）。从这些中，构建了一个包含 6 个 URGs 的预后标志物。纳入临床病理参数的列线图在 1、3 和 5 年时分别产生了令人印象深刻的 AUC 值 0.88、0.93 和 0.95。针对预后标志物中 E3 泛素连接酶 FBXO42 的功能实验揭示了其依赖于 TP53 的促进神经母细胞瘤细胞增殖作用。总之，我们的泛素化相关预后模型可有力预测患者的预后，指导临床决策。此外，FBXO42 的新发现的促增殖作用为理解神经母细胞瘤的分子机制提供了新的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/df5cf44840c2/41598_2024_69760_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/df5cf44840c2/41598_2024_69760_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/c0feddbdee7d/41598_2024_69760_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/24c2110882fc/41598_2024_69760_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/c74092851f64/41598_2024_69760_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/175857c55ce2/41598_2024_69760_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c5/11319589/df5cf44840c2/41598_2024_69760_Fig7_HTML.jpg

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