Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Xiaobo, Feng, Li, Yin, Yunfan, Yu, Chune, He, Xiujing, Zhu, Jiao, Zhang, Ming, Yu, Jing, Xu, Mingqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
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
_version_ 1784589787255013376
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
work_keys_str_mv AT zhengxiaobo comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT fengli comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT yinyunfan comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT yuchune comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT hexiujing comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT zhujiao comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT zhangming comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT yujing comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer
AT xumingqing comprehensiveanalysisofaberrantalternativesplicingrelatedtocarcinogenesisandprognosisofpapillarythyroidcancer