Features of alternative splicing in stomach adenocarcinoma and their clinical implication: a research based on massive sequencing data

Yuanyuan Zhang,Yun Han,Simiao Chen,Jie Jiang,Shengling Ma,Haolong Lin,Qian Niu,Xingyu Liu

doi:10.1186/s12864-020-06997-x

Yuanyuan Zhang, Yun Han + Show 6 more

Open Access

https://doi.org/10.1186/s12864-020-06997-x

Copy DOI

Abstract

BackgroundAlternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.Results2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.ConclusionsIn our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

Highlights

Alternative splicing (AS) offers a main mechanism to form protein polymorphism
A total of 157 alternate acceptor (AA) events in 153 genes, 174 alternate donor (AD) events in 164 genes, 461 alternate promoter (AP) events in 304 genes, 297 alternate terminator (AT) events in 203 genes, 805 exon skip (ES) events in 660 genes, 18 mutually exclusive exon (ME) events in 18 genes, and 130 retained intron (RI) events in 113 genes were identified as prognostic AS events (P < 0.05) (Fig. 1b, Additional file 2)
Prognostic signatures for stomach adenocarcinoma (STAD) patients By applying the least absolute shrinkage and selection operator (LASSO) Cox analysis following univariate Cox, which aims to filter out redundant genes and prevent overfitting of the model, we developed seven types of optimal prognostic signatures based on AA, AD, AP, AT, ES, ME and RI (Fig. 5, Table 1)

Summary

Introduction

Alternative splicing (AS) offers a main mechanism to form protein polymorphism. Significant progress has been made in the study of epidemiology, pathological mechanisms and Eukaryotic cells produce various regulatory changes and perform complex functions to adapt to changes in the environment, largely due to the diversity of proteins. A common mechanism is that a limited number of gene sets. Zhang et al BMC Genomics (2020) 21:580 produce a large number of mRNA isoforms through alternative splicing of pre-mRNA [5]. Alternative splicing causes the premature occurrence of termination codon in mRNA, which degrades immediately upon discovery to prevent its translation [9]. Alternative splicing is a key biological process in cells, and different mRNA splicing isoforms make the final protein products perform different functions

Methods

Results

Discussion

Conclusion