Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma

Metastasis is the major cause of hepatocellular carcinoma (HCC) mortality. Unfortunately, there are few reports on effective biomarkers for HCC metastasis. This study aimed to discover potential key genes of HCC, which could provide new insights for HCC metastasis. GEO (Gene Expression Omnibus) micr...

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Autores principales:	Shuai Li, Jingyuan Zhao, Linlin Lv, Deshi Dong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hepatocellular carcinoma metastasis TYMS prognostic biomarker bioinformatics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2fc7379849724f298daa965c39dc6cc1
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spelling	oai:doaj.org-article:2fc7379849724f298daa965c39dc6cc12021-11-09T05:37:19ZIdentification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma2234-943X10.3389/fonc.2021.762821https://doaj.org/article/2fc7379849724f298daa965c39dc6cc12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.762821/fullhttps://doaj.org/toc/2234-943XMetastasis is the major cause of hepatocellular carcinoma (HCC) mortality. Unfortunately, there are few reports on effective biomarkers for HCC metastasis. This study aimed to discover potential key genes of HCC, which could provide new insights for HCC metastasis. GEO (Gene Expression Omnibus) microarray and TCGA (The Cancer Genome Atlas) datasets were integrated to screen for candidate genes involved in HCC metastasis. Differentially expressed genes (DEGs) were screened, and then we performed enrichment analysis of Gene Ontology (GO), together with Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction network was then built and analyzed utilizing STRING and Cytoscape, followed by the identification of 10 hub genes by cytoHubba. Four genes were associated with survival, their prognostic value was verified by prognostic signature analysis. Thymidylate synthase (TYMS) gene was identified as significant HCC metastasis-associated genes after mRNA expression validation and IHC analysis. TYMS silencing in HCC cells remarkedly inhibited growth and invasion. Finally, we found TYMS silencing dramatically decrease DNA synthesis and extracellular matrix (ECM) degradation, resulting in the inhibition of HCC metastasis, indicating TYMS had close associations with HCC development. These findings provided new insights into HCC metastasis and identified candidate gene prognosis signatures for HCC metastasis.Shuai LiJingyuan ZhaoLinlin LvDeshi DongFrontiers Media S.A.articlehepatocellular carcinomametastasisTYMSprognostic biomarkerbioinformaticsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma metastasis TYMS prognostic biomarker bioinformatics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocellular carcinoma metastasis TYMS prognostic biomarker bioinformatics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Shuai Li Jingyuan Zhao Linlin Lv Deshi Dong Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
description	Metastasis is the major cause of hepatocellular carcinoma (HCC) mortality. Unfortunately, there are few reports on effective biomarkers for HCC metastasis. This study aimed to discover potential key genes of HCC, which could provide new insights for HCC metastasis. GEO (Gene Expression Omnibus) microarray and TCGA (The Cancer Genome Atlas) datasets were integrated to screen for candidate genes involved in HCC metastasis. Differentially expressed genes (DEGs) were screened, and then we performed enrichment analysis of Gene Ontology (GO), together with Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction network was then built and analyzed utilizing STRING and Cytoscape, followed by the identification of 10 hub genes by cytoHubba. Four genes were associated with survival, their prognostic value was verified by prognostic signature analysis. Thymidylate synthase (TYMS) gene was identified as significant HCC metastasis-associated genes after mRNA expression validation and IHC analysis. TYMS silencing in HCC cells remarkedly inhibited growth and invasion. Finally, we found TYMS silencing dramatically decrease DNA synthesis and extracellular matrix (ECM) degradation, resulting in the inhibition of HCC metastasis, indicating TYMS had close associations with HCC development. These findings provided new insights into HCC metastasis and identified candidate gene prognosis signatures for HCC metastasis.
format	article
author	Shuai Li Jingyuan Zhao Linlin Lv Deshi Dong
author_facet	Shuai Li Jingyuan Zhao Linlin Lv Deshi Dong
author_sort	Shuai Li
title	Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
title_short	Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
title_full	Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
title_fullStr	Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
title_full_unstemmed	Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
title_sort	identification and validation of tyms as a potential biomarker for risk of metastasis development in hepatocellular carcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2fc7379849724f298daa965c39dc6cc1
work_keys_str_mv	AT shuaili identificationandvalidationoftymsasapotentialbiomarkerforriskofmetastasisdevelopmentinhepatocellularcarcinoma AT jingyuanzhao identificationandvalidationoftymsasapotentialbiomarkerforriskofmetastasisdevelopmentinhepatocellularcarcinoma AT linlinlv identificationandvalidationoftymsasapotentialbiomarkerforriskofmetastasisdevelopmentinhepatocellularcarcinoma AT deshidong identificationandvalidationoftymsasapotentialbiomarkerforriskofmetastasisdevelopmentinhepatocellularcarcinoma
_version_	1718441282927329280

Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma

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