Prognostic Potential of Alternative Splicing Markers in Endometrial Cancer

被引：14

作者：

Wang, Qian ^{[1
]}

Xu, Teng ^{[2
,3
]}

Tong, Yu ^{[1
]}

Wu, Jianbo ^{[4
]}

Zhu, Weijian ^{[4
]}

Lu, Zhongqiu ^{[5
]}

Ying, Jianchao ^{[4
,5
]}

机构：

[1] Wenzhou Med Univ, Clin Inst 3, Wenzhou Peoples Hosp, Dept Clin Lab, Wenzhou, Peoples R China

[2] Tongji Univ, Sch Med, Shanghai East Hosp, Res Ctr Translat Med, Shanghai, Peoples R China

[3] Inner Mogolia Med Univ, Baotou Cent Hosp, Inst Translat Med, Baotou, Peoples R China

[4] Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou 325000, Peoples R China

[5] Wenzhou Med Univ, Affiliated Hosp 1, Inst Emergency Med, Wenzhou 325000, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2019年 / 18卷

基金：

中国国家自然科学基金;

关键词：

PATHWAY; PROTEIN; IDENTIFICATION; EXPRESSION; SIGNATURE; TIMP1; RISK; GENE;

D O I：

10.1016/j.omtn.2019.10.027

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Alternative splicing (AS), an important post-transcriptional regulatory mechanism that regulates the translation of mRNA isoforms and generates protein diversity, has been widely demonstrated to be associated with oncogenic processes. In this study, we systematically analyzed genome-wide AS patterns to explore the prognostic implications of AS in endometrial cancer (EC). A total of 2,324 AS events were identified as being associated with the overall survival of EC patients, and eleven of these events were further selected using a random forest algorithm. With the implementation of a generalized, boosted regression model, a prognostic AS model that aggregated these eleven markers was ultimately established with high performance for risk stratification in EC patients. Functional analysis of these eleven AS markers revealed various potential signaling pathways implicated in the progression of EC. Splicing network analysis demonstrated the notable correlation between the expression of splicing factors and AS markers in EC and further determined eight candidate splicing factors that could be therapeutic targets for EC. Taken together, the results of this study present the utility of AS profiling in identifying biomarkers for the prognosis of EC and provide comprehensive insight into the molecular mechanisms involved in EC processes.

引用

页码：1039 / 1048

页数：10

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