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Article

Genome-Wide Analysis of Prognostic Alternative Splicing Signature and Splicing Factors in Lung Adenocarcinoma

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Epigenome Research Center, China Medical University Hospital, 404 Taichung, Taiwan
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Department of Laboratory Medicine, China Medical University Hospital, 404 Taichung, Taiwan
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Center for Precision Medicine, China Medical University Hospital, 404 Taichung, Taiwan
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Department of Medical Laboratory Science and Biotechnology, China Medical University, 404 Taichung, Taiwan
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Department of Thoracic Surgery, China Medical University Hospital, 404 Taichung, Taiwan
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School of Medicine, China Medical University, 404 Taichung, Taiwan
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Department of Bioinformatics and Medical Engineering, Asia University, 413 Taichung, Taiwan
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Author to whom correspondence should be addressed.
Genes 2020, 11(11), 1300; https://doi.org/10.3390/genes11111300
Received: 26 September 2020 / Revised: 29 October 2020 / Accepted: 29 October 2020 / Published: 31 October 2020
(This article belongs to the Section Human Genomics and Genetic Diseases)
Analysis of The Cancer Genome Atlas data revealed that alternative splicing (AS) events could serve as prognostic biomarkers in various cancer types. This study examined lung adenocarcinoma (LUAD) tissues for AS and assessed AS events as potential indicators of prognosis in our cohort. RNA sequencing and bioinformatics analysis were performed. We used SUPPA2 to analyze the AS profiles. Using univariate Cox regression analysis, overall survival (OS)-related AS events were identified. Genes relating to the OS-related AS events were imported into Cytoscape, and the CytoHubba application was run. OS-related splicing factors (SFs) were explored using the log-rank test. The relationship between the percent spliced-in value of the OS-related AS events and SF expression was identified by Spearman correlation analysis. We found 1957 OS-related AS events in 1151 genes, and most were protective factors. Alternative first exon splicing was the most frequent type of splicing event. The hub genes in the gene network of the OS-related AS events were FBXW11, FBXL5, KCTD7, UBB and CDC27. The area under the curve of the MIX prediction model was 0.847 for 5-year survival based on seven OS-related AS events. Overexpression of SFs CELF2 and SRSF5 was associated with better OS. We constructed a correlation network between SFs and OS-related AS events. In conclusion, we identified prognostic predictors using AS events that stratified LUAD patients into high- and low-risk groups. The discovery of the splicing networks in this study provides an insight into the underlying mechanisms. View Full-Text
Keywords: lung adenocarcinoma; RNA sequencing; alternative splicing; splicing factor lung adenocarcinoma; RNA sequencing; alternative splicing; splicing factor
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MDPI and ACS Style

Chang, Y.-S.; Tu, S.-J.; Chiang, H.-S.; Yen, J.-C.; Lee, Y.-T.; Fang, H.-Y.; Chang, J.-G. Genome-Wide Analysis of Prognostic Alternative Splicing Signature and Splicing Factors in Lung Adenocarcinoma. Genes 2020, 11, 1300. https://doi.org/10.3390/genes11111300

AMA Style

Chang Y-S, Tu S-J, Chiang H-S, Yen J-C, Lee Y-T, Fang H-Y, Chang J-G. Genome-Wide Analysis of Prognostic Alternative Splicing Signature and Splicing Factors in Lung Adenocarcinoma. Genes. 2020; 11(11):1300. https://doi.org/10.3390/genes11111300

Chicago/Turabian Style

Chang, Ya-Sian, Siang-Jyun Tu, Hui-Shan Chiang, Ju-Chen Yen, Ya-Ting Lee, Hsin-Yuan Fang, and Jan-Gowth Chang. 2020. "Genome-Wide Analysis of Prognostic Alternative Splicing Signature and Splicing Factors in Lung Adenocarcinoma" Genes 11, no. 11: 1300. https://doi.org/10.3390/genes11111300

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