Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia
BackgroundBiliary atresia (BA) is a life-threatening disorder, which is characterized by the obliteration of biliary tracts. Heparan sulfate proteoglycans (HSPGs) are important regulators in liver diseases. Whether HSPGs participate in the development of BA is poorly understood.MethodsRNA-seq datase...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1065521/full |
| _version_ | 1797934927495299072 |
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| author | Zequan Ding Wenyu Song Wei Zhu Hua Xie Zhongxian Zhu Weibing Tang |
| author_facet | Zequan Ding Wenyu Song Wei Zhu Hua Xie Zhongxian Zhu Weibing Tang |
| author_sort | Zequan Ding |
| collection | DOAJ |
| description | BackgroundBiliary atresia (BA) is a life-threatening disorder, which is characterized by the obliteration of biliary tracts. Heparan sulfate proteoglycans (HSPGs) are important regulators in liver diseases. Whether HSPGs participate in the development of BA is poorly understood.MethodsRNA-seq dataset GSE122340, including 171 BA and 7 normal liver tissue, was integrated for bioinformatic analysis. R function “wilcox.test” was used to compare HSPGs expression levels, and “cor.test” was used to evaluate the correlation analysis. MCPcounter was used to assess the abundance of immunocytes. Molecular subtypes of BA were clustered via NMF clustering and LASSO regression was applied to screen hub HSPGs genes in BA clusters. RT-PCR analysis was used to assess the expression of hub HSPGs in BA liver. Immunohistochemical staining and immunofluorescence assay were used to evaluated the location and expression of hub HSPGs in BA liver tissue.ResultsMajority of HSPGs was up-regulated in BA and correlated with liver fibrosis and ductular reaction markers. The abundance of immunocytes was higher in BA and associated with HSPGs. Based on the expression of HSPGs, BA patients were classified into 3 subtypes (C1, C2, and C3). Pathway enrichment analysis revealed C1 subtype had severe liver injury with SDC4 identified as the hub gene, while C3 subtype presented relatively normal liver condition with GPC3 identified as the hub gene. RT-PCR analysis demonstrated the expression levels of 2 hub genes in BA liver tissue with different jaundice clearance standards. Immunohistochemical staining and immunofluorescence assay showed that SDC4 was mostly expressed in ductular reaction area, while GPC3 was mostly expressed in hepatocytes.ConclusionMajority of HSPGs are aberrant expressed in BA. The subtype hub gene SDC4 and GPC3 might be used as a potential indicator for different types of prognosis. |
| first_indexed | 2024-04-10T18:06:29Z |
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| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-10T18:06:29Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-d10687e8d05d43988261140e3475c42b2023-02-02T12:58:56ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-02-011110.3389/fped.2023.10655211065521Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresiaZequan Ding0Wenyu Song1Wei Zhu2Hua Xie3Zhongxian Zhu4Weibing Tang5Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, ChinaBackgroundBiliary atresia (BA) is a life-threatening disorder, which is characterized by the obliteration of biliary tracts. Heparan sulfate proteoglycans (HSPGs) are important regulators in liver diseases. Whether HSPGs participate in the development of BA is poorly understood.MethodsRNA-seq dataset GSE122340, including 171 BA and 7 normal liver tissue, was integrated for bioinformatic analysis. R function “wilcox.test” was used to compare HSPGs expression levels, and “cor.test” was used to evaluate the correlation analysis. MCPcounter was used to assess the abundance of immunocytes. Molecular subtypes of BA were clustered via NMF clustering and LASSO regression was applied to screen hub HSPGs genes in BA clusters. RT-PCR analysis was used to assess the expression of hub HSPGs in BA liver. Immunohistochemical staining and immunofluorescence assay were used to evaluated the location and expression of hub HSPGs in BA liver tissue.ResultsMajority of HSPGs was up-regulated in BA and correlated with liver fibrosis and ductular reaction markers. The abundance of immunocytes was higher in BA and associated with HSPGs. Based on the expression of HSPGs, BA patients were classified into 3 subtypes (C1, C2, and C3). Pathway enrichment analysis revealed C1 subtype had severe liver injury with SDC4 identified as the hub gene, while C3 subtype presented relatively normal liver condition with GPC3 identified as the hub gene. RT-PCR analysis demonstrated the expression levels of 2 hub genes in BA liver tissue with different jaundice clearance standards. Immunohistochemical staining and immunofluorescence assay showed that SDC4 was mostly expressed in ductular reaction area, while GPC3 was mostly expressed in hepatocytes.ConclusionMajority of HSPGs are aberrant expressed in BA. The subtype hub gene SDC4 and GPC3 might be used as a potential indicator for different types of prognosis.https://www.frontiersin.org/articles/10.3389/fped.2023.1065521/fullheparan sulfate proteoglycanbiliary atresialiver fibrosisductular reactionimmunocytes infiltrationmolecular classification |
| spellingShingle | Zequan Ding Wenyu Song Wei Zhu Hua Xie Zhongxian Zhu Weibing Tang Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia Frontiers in Pediatrics heparan sulfate proteoglycan biliary atresia liver fibrosis ductular reaction immunocytes infiltration molecular classification |
| title | Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia |
| title_full | Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia |
| title_fullStr | Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia |
| title_full_unstemmed | Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia |
| title_short | Bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia |
| title_sort | bioinformatics analysis identifies heparan sulfate proteoglycans acting as different progress subtypes of biliary atresia |
| topic | heparan sulfate proteoglycan biliary atresia liver fibrosis ductular reaction immunocytes infiltration molecular classification |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1065521/full |
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