Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer
Ovarian cancer (OV) is characterized by high incidence and poor prognosis. Increasing evidence indicates that aberrant alternative splicing (AS) events are associated with the pathogenesis of cancer. We examined prognosis-related alternative splicing events and constructed a clinically applicable mo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | RNA Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15476286.2022.2113148 |
| _version_ | 1797403968247169024 |
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| author | Shizhi Wang Shiyuan Wang Xing Zhang Dan Meng Qianqian Xia Shuqian Xie Siyuan Shen Bingjia Yu Jing Hu Haohan Liu Wenjing Yan |
| author_facet | Shizhi Wang Shiyuan Wang Xing Zhang Dan Meng Qianqian Xia Shuqian Xie Siyuan Shen Bingjia Yu Jing Hu Haohan Liu Wenjing Yan |
| author_sort | Shizhi Wang |
| collection | DOAJ |
| description | Ovarian cancer (OV) is characterized by high incidence and poor prognosis. Increasing evidence indicates that aberrant alternative splicing (AS) events are associated with the pathogenesis of cancer. We examined prognosis-related alternative splicing events and constructed a clinically applicable model to predict patients’ outcomes. Public database including The Cancer Genome Atlas (TCGA), TCGA SpliceSeq, and the Genomics of Drug Sensitivity in Cancer databases were used to detect the AS expression, immune cell infiltration and IC50. The prognosis-related AS model was constructed and validated by using Cox regression, LASSO regression, C-index, calibration plots, and ROC curves. A total of eight AS events (including FLT3LG|50942|AP) were selected to establish the prognosis-related AS model. Compared with high-risk group, low-risk group had a better outcome (P = 1.794e-06), was more sensitive to paclitaxel (P = 0.022), and higher proportions of plasma cells. We explored the upstream regulatory mechanisms of prognosis-related AS and found that two splicing factor and 156 tag single nucleotide polymorphisms may be involved in the regulation of prognosis-related AS. In order to assess patient prognosis more comprehensively, we constructed a clinically applicable model combining risk score and clinicopathological features, and the 1 -, and 3-year AUCs of the clinically applicable model were 0.812, and 0.726, which were 7.5% and 3.3% higher than that of the risk score. We constructed a prognostic signature for OV patients and comprehensively analysed the regulatory characteristics of the prognostic AS events in OV. |
| first_indexed | 2024-03-09T02:47:21Z |
| format | Article |
| id | doaj.art-67d9306eeee246d4b6430d304b74347e |
| institution | Directory Open Access Journal |
| issn | 1547-6286 1555-8584 |
| language | English |
| last_indexed | 2024-03-09T02:47:21Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj.art-67d9306eeee246d4b6430d304b74347e2023-12-05T16:09:51ZengTaylor & Francis GroupRNA Biology1547-62861555-85842022-12-011911007101810.1080/15476286.2022.21131482113148Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancerShizhi WangShiyuan Wang0Xing Zhang1Dan Meng2Qianqian Xia3Shuqian Xie4Siyuan Shen5Bingjia Yu6Jing Hu7Haohan Liu8Wenjing Yan9Southeast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversitySoutheast UniversityOvarian cancer (OV) is characterized by high incidence and poor prognosis. Increasing evidence indicates that aberrant alternative splicing (AS) events are associated with the pathogenesis of cancer. We examined prognosis-related alternative splicing events and constructed a clinically applicable model to predict patients’ outcomes. Public database including The Cancer Genome Atlas (TCGA), TCGA SpliceSeq, and the Genomics of Drug Sensitivity in Cancer databases were used to detect the AS expression, immune cell infiltration and IC50. The prognosis-related AS model was constructed and validated by using Cox regression, LASSO regression, C-index, calibration plots, and ROC curves. A total of eight AS events (including FLT3LG|50942|AP) were selected to establish the prognosis-related AS model. Compared with high-risk group, low-risk group had a better outcome (P = 1.794e-06), was more sensitive to paclitaxel (P = 0.022), and higher proportions of plasma cells. We explored the upstream regulatory mechanisms of prognosis-related AS and found that two splicing factor and 156 tag single nucleotide polymorphisms may be involved in the regulation of prognosis-related AS. In order to assess patient prognosis more comprehensively, we constructed a clinically applicable model combining risk score and clinicopathological features, and the 1 -, and 3-year AUCs of the clinically applicable model were 0.812, and 0.726, which were 7.5% and 3.3% higher than that of the risk score. We constructed a prognostic signature for OV patients and comprehensively analysed the regulatory characteristics of the prognostic AS events in OV.http://dx.doi.org/10.1080/15476286.2022.2113148alternative splicingprognostic factortumour immune microenvironmentclinically applicable modelovarian cancer |
| spellingShingle | Shizhi Wang Shiyuan Wang Xing Zhang Dan Meng Qianqian Xia Shuqian Xie Siyuan Shen Bingjia Yu Jing Hu Haohan Liu Wenjing Yan Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer RNA Biology alternative splicing prognostic factor tumour immune microenvironment clinically applicable model ovarian cancer |
| title | Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer |
| title_full | Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer |
| title_fullStr | Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer |
| title_full_unstemmed | Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer |
| title_short | Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer |
| title_sort | comprehensive analysis of prognosis related alternative splicing events in ovarian cancer |
| topic | alternative splicing prognostic factor tumour immune microenvironment clinically applicable model ovarian cancer |
| url | http://dx.doi.org/10.1080/15476286.2022.2113148 |
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