Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma
Hepatoblastoma (HB) is the most common liver tumor in the pediatric population, with typically poor outcomes for advanced-stage or chemotherapy-refractory HB patients. The objective of this study was to identify genes involved in HB pathogenesis via microarray analysis and subsequent experimental va...
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| Format: | Article |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.631982/full |
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| author | Linlin Tian Linlin Tian Linlin Tian Tong Chen Tong Chen Tong Chen Jiaju Lu Jiaju Lu Jianguo Yan Yuting Zhang Peifang Qin Sentai Ding Sentai Ding Yali Zhou Yali Zhou |
| author_facet | Linlin Tian Linlin Tian Linlin Tian Tong Chen Tong Chen Tong Chen Jiaju Lu Jiaju Lu Jianguo Yan Yuting Zhang Peifang Qin Sentai Ding Sentai Ding Yali Zhou Yali Zhou |
| author_sort | Linlin Tian |
| collection | DOAJ |
| description | Hepatoblastoma (HB) is the most common liver tumor in the pediatric population, with typically poor outcomes for advanced-stage or chemotherapy-refractory HB patients. The objective of this study was to identify genes involved in HB pathogenesis via microarray analysis and subsequent experimental validation. We identified 856 differentially expressed genes (DEGs) between HB and normal liver tissue based on two publicly available microarray datasets (GSE131329 and GSE75271) after data merging and batch effect correction. Protein–protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were conducted to explore HB-related critical modules and hub genes. Subsequently, Gene Ontology (GO) analysis was used to reveal critical biological functions in the initiation and progression of HB. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that genes involved in cell cycle phase transition and the PI3K/AKT signaling were associated with HB. The intersection of hub genes identified by both PPI and WGCNA analyses revealed five potential candidate genes. Based on receiver operating characteristic (ROC) curve analysis and reports in the literature, we selected CCNA2, CDK1, and CDC20 as key genes of interest to validate experimentally. CCNA2, CDK1, or CDC20 small interfering RNA (siRNA) knockdown inhibited aggressive biological properties of both HepG2 and HuH-6 cell lines in vitro. In conclusion, we identified CCNA2, CDK1, and CDC20 as new potential therapeutic biomarkers for HB, providing novel insights into important and viable targets in future HB treatment. |
| first_indexed | 2024-12-22T20:56:55Z |
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| id | doaj.art-f26321c066c841e5b4dc104e53d74edc |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-22T20:56:55Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f26321c066c841e5b4dc104e53d74edc2022-12-21T18:12:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.631982631982Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in HepatoblastomaLinlin Tian0Linlin Tian1Linlin Tian2Tong Chen3Tong Chen4Tong Chen5Jiaju Lu6Jiaju Lu7Jianguo Yan8Yuting Zhang9Peifang Qin10Sentai Ding11Sentai Ding12Yali Zhou13Yali Zhou14Department of Microbiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of General Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, ChinaDepartment of Microbiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, ChinaDepartment of Microbiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Microbiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, ChinaKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, ChinaHepatoblastoma (HB) is the most common liver tumor in the pediatric population, with typically poor outcomes for advanced-stage or chemotherapy-refractory HB patients. The objective of this study was to identify genes involved in HB pathogenesis via microarray analysis and subsequent experimental validation. We identified 856 differentially expressed genes (DEGs) between HB and normal liver tissue based on two publicly available microarray datasets (GSE131329 and GSE75271) after data merging and batch effect correction. Protein–protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were conducted to explore HB-related critical modules and hub genes. Subsequently, Gene Ontology (GO) analysis was used to reveal critical biological functions in the initiation and progression of HB. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that genes involved in cell cycle phase transition and the PI3K/AKT signaling were associated with HB. The intersection of hub genes identified by both PPI and WGCNA analyses revealed five potential candidate genes. Based on receiver operating characteristic (ROC) curve analysis and reports in the literature, we selected CCNA2, CDK1, and CDC20 as key genes of interest to validate experimentally. CCNA2, CDK1, or CDC20 small interfering RNA (siRNA) knockdown inhibited aggressive biological properties of both HepG2 and HuH-6 cell lines in vitro. In conclusion, we identified CCNA2, CDK1, and CDC20 as new potential therapeutic biomarkers for HB, providing novel insights into important and viable targets in future HB treatment.https://www.frontiersin.org/articles/10.3389/fcell.2021.631982/fullCCNA2CDC20CDK1hepatoblastomaPPIWGCNA |
| spellingShingle | Linlin Tian Linlin Tian Linlin Tian Tong Chen Tong Chen Tong Chen Jiaju Lu Jiaju Lu Jianguo Yan Yuting Zhang Peifang Qin Sentai Ding Sentai Ding Yali Zhou Yali Zhou Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma Frontiers in Cell and Developmental Biology CCNA2 CDC20 CDK1 hepatoblastoma PPI WGCNA |
| title | Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma |
| title_full | Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma |
| title_fullStr | Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma |
| title_full_unstemmed | Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma |
| title_short | Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma |
| title_sort | integrated protein protein interaction and weighted gene co expression network analysis uncover three key genes in hepatoblastoma |
| topic | CCNA2 CDC20 CDK1 hepatoblastoma PPI WGCNA |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.631982/full |
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