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Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer
As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544310/ https://www.ncbi.nlm.nih.gov/pubmed/34628367 http://dx.doi.org/10.18632/aging.203608 |
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author | Zheng, Xiaobo Feng, Li Yin, Yunfan Yu, Chune He, Xiujing Zhu, Jiao Zhang, Ming Yu, Jing Xu, Mingqing |
author_facet | Zheng, Xiaobo Feng, Li Yin, Yunfan Yu, Chune He, Xiujing Zhu, Jiao Zhang, Ming Yu, Jing Xu, Mingqing |
author_sort | Zheng, Xiaobo |
collection | PubMed |
description | As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its correlation with matched clinical information was performed using a 389 PTC patient cohort from the project of The Cancer Genome Atlas (TCGA). We identified 1,925 cancer-associated AS events (CASEs) by comparing paired tumors and neighboring healthy tissues. Parent genes with CASEs remarkably enriched in the pathways were linked with carcinogenesis, such as P53, KRAS, IL6-JAK-STAT3, apoptosis, and MYC signaling. The regulatory networks of AS implied an obvious correlation between the expression of splicing factor and CASE. We identified eight CASEs as predictors for overall survival (OS) and disease-free survival (DFS). The established risk score model based on DFS-associated CASEs successfully predicted the prognosis of PTC patients. From the unsupervised clustering analysis results, it is found that different clusters based on AS correlated with prognosis, molecular features, and immune characteristics. Taken together, the comprehensive genome-wide AS landscape analysis in PTC showed new AS events linked with tumorigenesis and prognosis, which provide new insights for clinical monitoring and therapy for PTC. |
format | Online Article Text |
id | pubmed-8544310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-85443102021-10-26 Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer Zheng, Xiaobo Feng, Li Yin, Yunfan Yu, Chune He, Xiujing Zhu, Jiao Zhang, Ming Yu, Jing Xu, Mingqing Aging (Albany NY) Research Paper As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its correlation with matched clinical information was performed using a 389 PTC patient cohort from the project of The Cancer Genome Atlas (TCGA). We identified 1,925 cancer-associated AS events (CASEs) by comparing paired tumors and neighboring healthy tissues. Parent genes with CASEs remarkably enriched in the pathways were linked with carcinogenesis, such as P53, KRAS, IL6-JAK-STAT3, apoptosis, and MYC signaling. The regulatory networks of AS implied an obvious correlation between the expression of splicing factor and CASE. We identified eight CASEs as predictors for overall survival (OS) and disease-free survival (DFS). The established risk score model based on DFS-associated CASEs successfully predicted the prognosis of PTC patients. From the unsupervised clustering analysis results, it is found that different clusters based on AS correlated with prognosis, molecular features, and immune characteristics. Taken together, the comprehensive genome-wide AS landscape analysis in PTC showed new AS events linked with tumorigenesis and prognosis, which provide new insights for clinical monitoring and therapy for PTC. Impact Journals 2021-10-08 /pmc/articles/PMC8544310/ /pubmed/34628367 http://dx.doi.org/10.18632/aging.203608 Text en Copyright: © 2021 Zheng et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zheng, Xiaobo Feng, Li Yin, Yunfan Yu, Chune He, Xiujing Zhu, Jiao Zhang, Ming Yu, Jing Xu, Mingqing Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
title | Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
title_full | Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
title_fullStr | Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
title_full_unstemmed | Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
title_short | Comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
title_sort | comprehensive analysis of aberrant alternative splicing related to carcinogenesis and prognosis of papillary thyroid cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544310/ https://www.ncbi.nlm.nih.gov/pubmed/34628367 http://dx.doi.org/10.18632/aging.203608 |
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