Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer

Abstract Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile...

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Autores principales:	Zeng-Hong Wu, Yun Tang, Yue Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/510bd6966b234b2a9c1a2ca79225bb08
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spelling	oai:doaj.org-article:510bd6966b234b2a9c1a2ca79225bb082021-12-02T11:35:53ZAlternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer10.1038/s41598-021-84403-62045-2322https://doaj.org/article/510bd6966b234b2a9c1a2ca79225bb082021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84403-6https://doaj.org/toc/2045-2322Abstract Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan–Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research.Zeng-Hong WuYun TangYue ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zeng-Hong Wu Yun Tang Yue Zhou Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
description	Abstract Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan–Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research.
format	article
author	Zeng-Hong Wu Yun Tang Yue Zhou
author_facet	Zeng-Hong Wu Yun Tang Yue Zhou
author_sort	Zeng-Hong Wu
title	Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
title_short	Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
title_full	Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
title_fullStr	Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
title_full_unstemmed	Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
title_sort	alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/510bd6966b234b2a9c1a2ca79225bb08
work_keys_str_mv	AT zenghongwu alternativesplicingeventsimplicatedincarcinogenesisandprognosisofthyroidglandcancer AT yuntang alternativesplicingeventsimplicatedincarcinogenesisandprognosisofthyroidglandcancer AT yuezhou alternativesplicingeventsimplicatedincarcinogenesisandprognosisofthyroidglandcancer
_version_	1718395819538776064

Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer

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