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EBioMedicine. 2018 Aug;34:46-60. doi: 10.1016/j.ebiom.2018.07.040. Epub 2018 Aug 18.

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas.

Author information

1
Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
2
Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
3
Department of General Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
4
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
5
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. Electronic address: chengang@gxmu.edu.cn.

Abstract

BACKGROUND:

Gastrointestinal pan-adenocarcinomas, which mainly include adenocarcinomas of the esophagus, stomach, colon, and rectum, place a heavy burden on society owing to their poor prognoses. Since aberrant alternative splicing (AS) are starting to be considered as efficacious signatures for tumor prognosis predicting and therapeutic targets, systematic analysis of AS events is urgent.

METHODS:

Prognosis-related AS events were selected by using univariate COX regression analysis. Gene functional enrichment analysis revealed the pathways enriched by prognosis-related AS. Then, prognostic signatures based on AS events were developed for prognosis prediction. Potential mechanism to regulate splicing events by splicing factors was analyzed via Pearson correlation and regulatory networks were constructed.

FINDINGS:

A total of 967, 918, 674, and 406 AS events were identified as prognosis-related AS events in esophagus, stomach, colon, and rectum adenocarcinomas, respectively. Survival-associated AS events were distinguishing in the four subtypes of adenocarcinoma. Furthermore, computational algorithm results indicated that perturbation of ribosome and ubiquitin-mediated proteolysis pathways were the potential molecular mechanisms corresponding to inferior prognoses. Most notably, several prognostic signatures based on AS events displayed moderate performance in prognosis predicting. The area under curve values of the time-dependent receiver operating characteristic were 0.961, 0.871, 0.870, and 0.890 in esophagus, stomach, colon, and rectum adenocarcinomas. Survival-associated splicing factors were submitted to construct the AS regulatory network, which could be an underlying mechanism of AS events.

INTERPRETATION:

AS may could be ideal indiactors in the prognosis of gastrointestinal pan-adenocarcinomas. Exploring interesting splicing regulatory networks is conducive to solve the puzzles of AS.

KEYWORDS:

Alternative splicing; Gastrointestinal pan-adenocarcinomas; Prognosis; Splicing factors

PMID:
30131306
PMCID:
PMC6116578
DOI:
10.1016/j.ebiom.2018.07.040
[Indexed for MEDLINE]
Free PMC Article

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