Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases
Background/Aims: Increasing evidences indicated the important roles of alternative splicing in the progression and prognosis of bladder urothelial carcinoma (BLCA). However, most previous research has focused on one or several alternative splicing events, without a comprehensive evaluation of the pr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-07-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/492094 |
| _version_ | 1818177319828717568 |
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| author | Rong-quan He Xian-guo Zhou Qiao-yong Yi Cai-wang Deng Jia-min Gao Gang Chen Qiu-yan Wang |
| author_facet | Rong-quan He Xian-guo Zhou Qiao-yong Yi Cai-wang Deng Jia-min Gao Gang Chen Qiu-yan Wang |
| author_sort | Rong-quan He |
| collection | DOAJ |
| description | Background/Aims: Increasing evidences indicated the important roles of alternative splicing in the progression and prognosis of bladder urothelial carcinoma (BLCA). However, most previous research has focused on one or several alternative splicing events, without a comprehensive evaluation of the prognostic value of splicing events in BLCA. In this study, we aimed to determine risk scores for predicting prognosis of BLCA patients based on splicing events. Methods: RNA-sequencing data and clinical information of BLCA patients were downloaded from The Cancer Genome Atlas, and data of splicing events were obtained from the SpliceSeq database. Univariate and multivariate Cox regression analyses were employed to identify survival-associated alternative spicing events (SASEs) and to calculate risk scores. Protein-protein interaction analysis of genes of the SASEs was performed using STRING, a database of known and predicted protein-protein interactions, and pathway enrichment analysis of the genes was implemented using the Database for Annotation, Visualization and Integrated Discovery (version 6.8). Receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to evaluate the clinical significance of genes from the SASEs for building a risk score in BLCA. Correlation between splicing events of splicing factors and non-splicing factors were analyzed with Pearson correlation coefficient. A potential regulatory network was then built using Cytoscape 3.5. Results: In total, 39,508 alternative splicing events in 317 patients with BLCA were analyzed, including 4,632 SASEs. The area under the curve of the ROC of risk score (all) was 0.748 for predicting survival status of BLCA patients. Low- and high-risk score groups classified using the median “risk score (all)” value displayed remarkably different survival time (Low vs. High = 3304.841±239.758 vs 1198.614±152.460 days). The potential regulatory network with SASEs of splicing factors and other genes was constructed, which might be part of the biological mechanisms associated with prognosis of BLCA patients. Conclusions: In this study, prognostic signatures constructed using splicing events could be used for predicting the prognosis of BLCA patients. |
| first_indexed | 2024-12-11T20:30:12Z |
| format | Article |
| id | doaj.art-8417cd5c7d0b411ea0faa9ea77dc71b6 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T20:30:12Z |
| publishDate | 2018-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-8417cd5c7d0b411ea0faa9ea77dc71b62022-12-22T00:51:51ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-07-014831355136810.1159/000492094492094Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 CasesRong-quan HeXian-guo ZhouQiao-yong YiCai-wang DengJia-min GaoGang ChenQiu-yan WangBackground/Aims: Increasing evidences indicated the important roles of alternative splicing in the progression and prognosis of bladder urothelial carcinoma (BLCA). However, most previous research has focused on one or several alternative splicing events, without a comprehensive evaluation of the prognostic value of splicing events in BLCA. In this study, we aimed to determine risk scores for predicting prognosis of BLCA patients based on splicing events. Methods: RNA-sequencing data and clinical information of BLCA patients were downloaded from The Cancer Genome Atlas, and data of splicing events were obtained from the SpliceSeq database. Univariate and multivariate Cox regression analyses were employed to identify survival-associated alternative spicing events (SASEs) and to calculate risk scores. Protein-protein interaction analysis of genes of the SASEs was performed using STRING, a database of known and predicted protein-protein interactions, and pathway enrichment analysis of the genes was implemented using the Database for Annotation, Visualization and Integrated Discovery (version 6.8). Receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to evaluate the clinical significance of genes from the SASEs for building a risk score in BLCA. Correlation between splicing events of splicing factors and non-splicing factors were analyzed with Pearson correlation coefficient. A potential regulatory network was then built using Cytoscape 3.5. Results: In total, 39,508 alternative splicing events in 317 patients with BLCA were analyzed, including 4,632 SASEs. The area under the curve of the ROC of risk score (all) was 0.748 for predicting survival status of BLCA patients. Low- and high-risk score groups classified using the median “risk score (all)” value displayed remarkably different survival time (Low vs. High = 3304.841±239.758 vs 1198.614±152.460 days). The potential regulatory network with SASEs of splicing factors and other genes was constructed, which might be part of the biological mechanisms associated with prognosis of BLCA patients. Conclusions: In this study, prognostic signatures constructed using splicing events could be used for predicting the prognosis of BLCA patients.https://www.karger.com/Article/FullText/492094Bladder urothelial carcinomaSplicing eventThe Cancer Genome Atlas (TCGA)Prognosis |
| spellingShingle | Rong-quan He Xian-guo Zhou Qiao-yong Yi Cai-wang Deng Jia-min Gao Gang Chen Qiu-yan Wang Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases Cellular Physiology and Biochemistry Bladder urothelial carcinoma Splicing event The Cancer Genome Atlas (TCGA) Prognosis |
| title | Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases |
| title_full | Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases |
| title_fullStr | Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases |
| title_full_unstemmed | Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases |
| title_short | Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases |
| title_sort | prognostic signature of alternative splicing events in bladder urothelial carcinoma based on spliceseq data from 317 cases |
| topic | Bladder urothelial carcinoma Splicing event The Cancer Genome Atlas (TCGA) Prognosis |
| url | https://www.karger.com/Article/FullText/492094 |
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