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Prognostic significance of survival-associated alternative splicing events in gastric cancer

机译:胃癌中存活相关替代剪接事件的预后意义

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摘要

Alternative splicing events are a major source of transcript and protein diversity in eukaryotes. Aberrant alternative splicing events have been increasingly reported in various cancers, including gastric cancer. To further explore the prognostic significance of alternative splicing events in gastric cancer patients, a comprehensive and systematic investigation was conducted by integrating alternative splicing event data and clinical information. Univariate Cox regression analysis identified 1383 alternative splicing events to be significantly associated with the overall survival of gastric cancer patients. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were performed for the development of prognostic signatures. The final prognostic signature based on all seven types of alternative splicing events can act as an independent prognostic indicator after multivariate adjustment of several clinical parameters. Furthermore, the correlation and function analysis identified CELF2, BAG2, RBFOX2, PTBP2 and QKI as hub splicing factors, and the focal adhesion signaling pathway was most significantly correlated with survival-associated alternative splicing events. The results of this study may establish a foundation for further research investigating the underlying mechanism of alternative splicing events in the progression of gastric cancer.
机译:替代剪接事件是真核生物中转录物和蛋白质多样性的主要来源。在各种癌症中越来越多地报道异常替代的剪接事件,包括胃癌。为了进一步探讨胃癌患者替代剪接事件的预后意义,通过整合替代剪接事件数据和临床信息来进行全面和系统的调查。单变量COX回归分析确定了1383个替代剪接事件,与胃癌患者的整体存活率显着相关。然后,对最低绝对的收缩和选择操作员(套索)和多变量COX分析进行用于开发预后签名。基于所有七种类型的替代剪接事件的最终预后签名可以作为几种临床参数的多变量调整后作为独立预后指示剂。此外,相关性和功能分析识别Celf2,Bag2,RBFOX2,PTBP2和QKI作为轮毂剪接因子,并且焦粘导信号通路与生存相关的替代剪接事件最显着相关。该研究的结果可以为进一步研究研究胃癌进展中的替代剪接事件的潜在机制来建立一个基础。

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