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基于机器学习方法的癌症预后剪接因子研究。

Study of prognostic splicing factors in cancer using machine learning approaches.

机构信息

School of Life Sciences, Zhengzhou University, No. 100, Kexue Avenue, Zhengzhou, Henan 450001, China.

Center for Computational Systems Medicine, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin St Suite 600, Houston, Texas 77030, United States.

出版信息

Hum Mol Genet. 2024 Jun 21;33(13):1131-1141. doi: 10.1093/hmg/ddae047.

Abstract

Splicing factors (SFs) are the major RNA-binding proteins (RBPs) and key molecules that regulate the splicing of mRNA molecules through binding to mRNAs. The expression of splicing factors is frequently deregulated in different cancer types, causing the generation of oncogenic proteins involved in cancer hallmarks. In this study, we investigated the genes that encode RNA-binding proteins and identified potential splicing factors that contribute to the aberrant splicing applying a random forest classification model. The result suggested 56 splicing factors were related to the prognosis of 13 cancers, two SF complexes in liver hepatocellular carcinoma, and one SF complex in esophageal carcinoma. Further systematic bioinformatics studies on these cancer prognostic splicing factors and their related alternative splicing events revealed the potential regulations in a cancer-specific manner. Our analysis found high ILF2-ILF3 expression correlates with poor prognosis in LIHC through alternative splicing. These findings emphasize the importance of SFs as potential indicators for prognosis or targets for therapeutic interventions. Their roles in cancer exhibit complexity and are contingent upon the specific context in which they operate. This recognition further underscores the need for a comprehensive understanding and exploration of the role of SFs in different types of cancer, paving the way for their potential utilization in prognostic assessments and the development of targeted therapies.

摘要

剪接因子(SFs)是主要的 RNA 结合蛋白(RBPs)和关键分子,通过与 mRNA 结合调节 mRNA 分子的剪接。剪接因子的表达在不同类型的癌症中经常失调,导致产生参与癌症标志的致癌蛋白。在这项研究中,我们通过随机森林分类模型研究了编码 RNA 结合蛋白的基因,并鉴定了有助于异常剪接的潜在剪接因子。结果表明,56 种剪接因子与 13 种癌症的预后相关,在肝癌中有两个 SF 复合物,在食管癌中有一个 SF 复合物。对这些癌症预后剪接因子及其相关的可变剪接事件进行进一步的系统生物信息学研究,揭示了癌症特异性的潜在调控机制。我们的分析发现,ILF2-ILF3 的高表达与 LIHC 中的不良预后通过可变剪接相关。这些发现强调了 SFs 作为预后指标或治疗干预靶点的重要性。它们在癌症中的作用具有复杂性,取决于它们在特定环境中的作用。这种认识进一步强调了需要全面理解和探索 SFs 在不同类型癌症中的作用,为它们在预后评估和靶向治疗中的潜在应用铺平了道路。

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