Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis

The prognosis of children with biliary atresia (BA) after Kasai operation remains difficult to predict, and liver fibrosis is closely related to the prognosis of children with BA. We aimed to find biomarkers for native liver survival (NLS) prediction by weighted gene co-expression network analysis (...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Meng Kong, Bo Xiang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	LECT2 prognosis native liver survival biliary atresia WGCNA Genetics QH426-470
Acceso en línea:	https://doaj.org/article/aa333f52ac924df79716ac3dab0909fd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aa333f52ac924df79716ac3dab0909fd
record_format	dspace
spelling	oai:doaj.org-article:aa333f52ac924df79716ac3dab0909fd2021-12-01T02:32:36ZIdentifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis1664-802110.3389/fgene.2021.760182https://doaj.org/article/aa333f52ac924df79716ac3dab0909fd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.760182/fullhttps://doaj.org/toc/1664-8021The prognosis of children with biliary atresia (BA) after Kasai operation remains difficult to predict, and liver fibrosis is closely related to the prognosis of children with BA. We aimed to find biomarkers for native liver survival (NLS) prediction by weighted gene co-expression network analysis (WGCNA). The biological processes and signal pathways that biomarkers involved in were further analyzed by bioinformatics. Quantitative Real-time PCR, Western blot and immunohistochemistry was performed to detect biomarkers expression. The relationship of biomarkers with clinicopathological characteristics of BA was also investigated. LECT2 was overexpressed or knockdown in LX-2 cells, and the expression of fibrogenic genes such as a-SMA and COL1A1 was quantified. We found that LECT2 mRNA expression was higher in BA liver tissues compared with normal liver tissues. Bioinformatics showed that LECT2 mainly played a fibrosis-promoting role in the development in BA by regulating bile acid metabolism and promoting inflammatory response. LECT2 immunohistochemistry scores of BA children were higher than control group (p = 0.001). Survival analysis revealed that LECT2 high expression is an unfavorable prognostic factor for native liver survival in BA patients. Additionally, the high LECT2 expression was an independent prognostic factor affecting native liver survival (HR 3.702, 95%CI:2.085–6.575, p = 0.001). LECT2 modulates TGF-β mediated a-SMA and COL1A1 expression in LX-2 cells. siRNA-LECT2 inhibits the expression of a-SMA and COL1A1 in LX-2 cells. Overexpression of LECT2 resulted in an increase in a-SMA and COL1A1 expression. Knockdown of LECT2 inhibits the proliferation and increase apoptosis in activated LX-2 cells. LECT2 may act as a new prognostic biomarker for native liver survival in BA patients.Meng KongBo XiangFrontiers Media S.A.articleLECT2prognosisnative liver survivalbiliary atresiaWGCNAGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	LECT2 prognosis native liver survival biliary atresia WGCNA Genetics QH426-470
spellingShingle	LECT2 prognosis native liver survival biliary atresia WGCNA Genetics QH426-470 Meng Kong Bo Xiang Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis
description	The prognosis of children with biliary atresia (BA) after Kasai operation remains difficult to predict, and liver fibrosis is closely related to the prognosis of children with BA. We aimed to find biomarkers for native liver survival (NLS) prediction by weighted gene co-expression network analysis (WGCNA). The biological processes and signal pathways that biomarkers involved in were further analyzed by bioinformatics. Quantitative Real-time PCR, Western blot and immunohistochemistry was performed to detect biomarkers expression. The relationship of biomarkers with clinicopathological characteristics of BA was also investigated. LECT2 was overexpressed or knockdown in LX-2 cells, and the expression of fibrogenic genes such as a-SMA and COL1A1 was quantified. We found that LECT2 mRNA expression was higher in BA liver tissues compared with normal liver tissues. Bioinformatics showed that LECT2 mainly played a fibrosis-promoting role in the development in BA by regulating bile acid metabolism and promoting inflammatory response. LECT2 immunohistochemistry scores of BA children were higher than control group (p = 0.001). Survival analysis revealed that LECT2 high expression is an unfavorable prognostic factor for native liver survival in BA patients. Additionally, the high LECT2 expression was an independent prognostic factor affecting native liver survival (HR 3.702, 95%CI:2.085–6.575, p = 0.001). LECT2 modulates TGF-β mediated a-SMA and COL1A1 expression in LX-2 cells. siRNA-LECT2 inhibits the expression of a-SMA and COL1A1 in LX-2 cells. Overexpression of LECT2 resulted in an increase in a-SMA and COL1A1 expression. Knockdown of LECT2 inhibits the proliferation and increase apoptosis in activated LX-2 cells. LECT2 may act as a new prognostic biomarker for native liver survival in BA patients.
format	article
author	Meng Kong Bo Xiang
author_facet	Meng Kong Bo Xiang
author_sort	Meng Kong
title	Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis
title_short	Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis
title_full	Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis
title_fullStr	Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis
title_full_unstemmed	Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis
title_sort	identifying biomarkers to predict the prognosis of biliary atresia by weighted gene co-expression network analysis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/aa333f52ac924df79716ac3dab0909fd
work_keys_str_mv	AT mengkong identifyingbiomarkerstopredicttheprognosisofbiliaryatresiabyweightedgenecoexpressionnetworkanalysis AT boxiang identifyingbiomarkerstopredicttheprognosisofbiliaryatresiabyweightedgenecoexpressionnetworkanalysis
_version_	1718405920889765888

Identifying Biomarkers to Predict the Prognosis of Biliary Atresia by Weighted Gene Co-Expression Network Analysis

Ejemplares similares