Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma

Abstract Splicing factors (SFs) play critical roles in the pathogenesis of various cancers through regulating tumor-associated alternative splicing (AS) events. However, the clinical value and biological functions of SFs in hepatocellular carcinoma (HCC) remain obscure. In this study, we identified...

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Autores principales:	Yue Wang, Fan Yang, Jiaqi Shang, Haitao He, Qing Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c60f315459654e03be1acd9c10f5efb7
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spelling	oai:doaj.org-article:c60f315459654e03be1acd9c10f5efb72021-12-02T16:31:48ZIntegrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma10.1038/s41598-021-94701-82045-2322https://doaj.org/article/c60f315459654e03be1acd9c10f5efb72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94701-8https://doaj.org/toc/2045-2322Abstract Splicing factors (SFs) play critical roles in the pathogenesis of various cancers through regulating tumor-associated alternative splicing (AS) events. However, the clinical value and biological functions of SFs in hepatocellular carcinoma (HCC) remain obscure. In this study, we identified 40 dysregulated SFs in HCC and established a prognostic model composed of four SFs (DNAJC6, ZC3H13, IGF2BP3, DDX19B). The predictive efficiency and independence of the prognostic model were confirmed to be satisfactory. Gene Set Enrichment Analysis (GSEA) illustrated the risk score calculated by our prognostic model was significantly associated with multiple cancer-related pathways and metabolic processes. Furthermore, we constructed the SFs-AS events regulatory network and extracted 108 protein-coding genes from the network for following functional explorations. Protein–protein interaction (PPI) network delineated the potential interactions among these 108 protein-coding genes. GO and KEGG pathway analyses investigated ontology gene sets and canonical pathways enriched by these 108 protein-coding genes. Overlapping the results of GSEA and KEGG, seven pathways were identified to be potential pathways regulated by our prognostic model through triggering aberrant AS events in HCC. In conclusion, the present study established an effective prognostic model based on SFs for HCC patients. Functional explorations of SFs and SFs-associated AS events provided directions to explore biological functions and mechanisms of SFs in HCC tumorigenesis.Yue WangFan YangJiaqi ShangHaitao HeQing YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yue Wang Fan Yang Jiaqi Shang Haitao He Qing Yang Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
description	Abstract Splicing factors (SFs) play critical roles in the pathogenesis of various cancers through regulating tumor-associated alternative splicing (AS) events. However, the clinical value and biological functions of SFs in hepatocellular carcinoma (HCC) remain obscure. In this study, we identified 40 dysregulated SFs in HCC and established a prognostic model composed of four SFs (DNAJC6, ZC3H13, IGF2BP3, DDX19B). The predictive efficiency and independence of the prognostic model were confirmed to be satisfactory. Gene Set Enrichment Analysis (GSEA) illustrated the risk score calculated by our prognostic model was significantly associated with multiple cancer-related pathways and metabolic processes. Furthermore, we constructed the SFs-AS events regulatory network and extracted 108 protein-coding genes from the network for following functional explorations. Protein–protein interaction (PPI) network delineated the potential interactions among these 108 protein-coding genes. GO and KEGG pathway analyses investigated ontology gene sets and canonical pathways enriched by these 108 protein-coding genes. Overlapping the results of GSEA and KEGG, seven pathways were identified to be potential pathways regulated by our prognostic model through triggering aberrant AS events in HCC. In conclusion, the present study established an effective prognostic model based on SFs for HCC patients. Functional explorations of SFs and SFs-associated AS events provided directions to explore biological functions and mechanisms of SFs in HCC tumorigenesis.
format	article
author	Yue Wang Fan Yang Jiaqi Shang Haitao He Qing Yang
author_facet	Yue Wang Fan Yang Jiaqi Shang Haitao He Qing Yang
author_sort	Yue Wang
title	Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
title_short	Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
title_full	Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
title_fullStr	Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
title_full_unstemmed	Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
title_sort	integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c60f315459654e03be1acd9c10f5efb7
work_keys_str_mv	AT yuewang integrativeanalysisrevealstheprognosticvalueandfunctionsofsplicingfactorsimplicatedinhepatocellularcarcinoma AT fanyang integrativeanalysisrevealstheprognosticvalueandfunctionsofsplicingfactorsimplicatedinhepatocellularcarcinoma AT jiaqishang integrativeanalysisrevealstheprognosticvalueandfunctionsofsplicingfactorsimplicatedinhepatocellularcarcinoma AT haitaohe integrativeanalysisrevealstheprognosticvalueandfunctionsofsplicingfactorsimplicatedinhepatocellularcarcinoma AT qingyang integrativeanalysisrevealstheprognosticvalueandfunctionsofsplicingfactorsimplicatedinhepatocellularcarcinoma
_version_	1718383899292205056

Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma

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