Prognostic Value and Potential Role of Alternative mRNA Splicing Events in Cervical Cancer.

Xiang-Yang Shao,Ying-Song Wu,Han Zhang,Lei Zheng,Jin Dong

doi:10.3389/fgene.2020.00726

Xiang-Yang Shao, Ying-Song Wu + Show 3 more

Open Access

https://doi.org/10.3389/fgene.2020.00726

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Abstract

BackgroundIncreasing evidence suggests that aberrant alternative splicing (AS) events are associated with progression of cancer. This study evaluated the prognostic value and clarify the role of AS events in cervical cancer (CC).MethodsBased on RNA-seq AS event data and clinical information of CC patients in The Cancer Genome Atlas (TCGA) database, we sought to identify prognosis-related AS events in this setting. We selected several survival-associated AS events to construct a prognostic predictor for CC through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. Moreover, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed on genes with prognosis-related AS events and constructed an AS-splicing factors (SFs) regulatory network.Results2770 AS events were significantly correlated with overall survival (OS). The area under the curve (AUC) values of receiver-operator characteristic curve (ROC) for the final prognostic predictor were 0.926, 0.946 and 0.902 at 3, 5, and 10 years, respectively. These values indicated efficiency in prognostic risk stratification for patients with CC. The final prognostic predictor was an independent predictor of OS (HR: 1.24; 95% CI: 1.020–1.504; P < 0.05). The AS-SFs correlation network may reveal an underlying regulatory mechanism of AS events.ConclusionAS events are essential participants in the prognosis of CC and hold great potentials for the prognostic stratification and development of treatment strategy.

Highlights

Mounting evidence shows that abnormal gene expression is closely related to the genesis and progression of tumors
alternative splicing (AS) events are mainly regulated by splicing factors (SFs), whose mutations (Salton et al, 2015) or changes in expression may cause AS abnormalities (Shilo et al, 2014; Sveen et al, 2016) and activation of oncogenes and tumorigenic pathways (Shilo et al, 2014; Koh et al, 2015; Salton et al, 2015; Dvinge et al, 2016)
We performed univariate Cox regression analysis to evaluate the connection between clinical characteristics and outcome in the The Cancer Genome Atlas (TCGA)-CC (Table 1)

Summary

Introduction

Mounting evidence shows that abnormal gene expression is closely related to the genesis and progression of tumors. Various studies have been focused on differences in gene expression to discover potential diagnostic, prognostic biomarkers and therapeutic targets in tumors (Weiskirchen, 2016). Some promising results have been found for cancers, most of those studies only concentrated on gene expression levels, ignoring the transcriptional structure regulated by alternative splicing (AS). AS events are mainly regulated by splicing factors (SFs), whose mutations (Salton et al, 2015) or changes in expression may cause AS abnormalities (Shilo et al, 2014; Sveen et al, 2016) and activation of oncogenes and tumorigenic pathways (Shilo et al, 2014; Koh et al, 2015; Salton et al, 2015; Dvinge et al, 2016). Increasing evidence suggests that aberrant alternative splicing (AS) events are associated with progression of cancer. This study evaluated the prognostic value and clarify the role of AS events in cervical cancer (CC)

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Conclusion