Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma
Background. Cancer stem cells (CSCs) are typically related to metastasis, recurrence, and drug resistance in malignant tumors. However, the biomarker and mechanism of CSCs need further exploration. This study is aimed at comprehensively depicting the stemness characteristics and identify a potential...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2022/1534593 |
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| author | Yangyang Zhang Ruike Zhang Lingxiu Zeng Haizhou Wang Ruyi Peng Meng Zhang Hailin Zhang Zhenwei Yang Liping Gao Meng Wang Jing Liu |
| author_facet | Yangyang Zhang Ruike Zhang Lingxiu Zeng Haizhou Wang Ruyi Peng Meng Zhang Hailin Zhang Zhenwei Yang Liping Gao Meng Wang Jing Liu |
| author_sort | Yangyang Zhang |
| collection | DOAJ |
| description | Background. Cancer stem cells (CSCs) are typically related to metastasis, recurrence, and drug resistance in malignant tumors. However, the biomarker and mechanism of CSCs need further exploration. This study is aimed at comprehensively depicting the stemness characteristics and identify a potential stemness-associated biomarker in hepatocellular carcinoma (HCC). Methods. The data of HCC patients from The Cancer Genome Atlas (TCGA) were collected and divided based on the mRNA expression-based stemness index (mRNAsi) in this study. Weighted gene coexpression network analysis (WGCNA) and the protein-protein interaction (PPI) network were performed, and the genes were screened through the Cytoscape software. Then, we constructed a prognostic expression signature using the multivariable Cox analysis and verified using the GEO and ICGC databases. Even more importantly, we used the three-dimensional (3D) fibrin gel to enrich the tumor-repopulating cells (TRCs) to validate the expression of the signature in CSCs by quantitative RT-PCR. Results. mRNAsi was significantly elevated in tumor and high-mRNAsi score was associated with poor overall survival in HCC. The positive stemness-associated (blue) module with 737 genes were screened based on WGCNA, and Budding uninhibited by benzimidazoles 1 (BUB1) was identified as the hub gene highly related to stemness in HCC. Then, the prognostic value and stemness characteristics were well validated in the ICGC and GSE14520 cohorts. Further analysis showed the expression of BUB1 was elevated in TRCs. Conclusion. BUB1, as a potential stemness-associated biomarker, could serve as a therapeutic CSCs-target and predicted the clinical outcomes of patients with HCC. |
| format | Article |
| id | doaj-art-63dbd9ba5e884668a1abbe96dcbc95ae |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-63dbd9ba5e884668a1abbe96dcbc95ae2025-02-03T01:32:27ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/1534593Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular CarcinomaYangyang Zhang0Ruike Zhang1Lingxiu Zeng2Haizhou Wang3Ruyi Peng4Meng Zhang5Hailin Zhang6Zhenwei Yang7Liping Gao8Meng Wang9Jing Liu10Department of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyBackground. Cancer stem cells (CSCs) are typically related to metastasis, recurrence, and drug resistance in malignant tumors. However, the biomarker and mechanism of CSCs need further exploration. This study is aimed at comprehensively depicting the stemness characteristics and identify a potential stemness-associated biomarker in hepatocellular carcinoma (HCC). Methods. The data of HCC patients from The Cancer Genome Atlas (TCGA) were collected and divided based on the mRNA expression-based stemness index (mRNAsi) in this study. Weighted gene coexpression network analysis (WGCNA) and the protein-protein interaction (PPI) network were performed, and the genes were screened through the Cytoscape software. Then, we constructed a prognostic expression signature using the multivariable Cox analysis and verified using the GEO and ICGC databases. Even more importantly, we used the three-dimensional (3D) fibrin gel to enrich the tumor-repopulating cells (TRCs) to validate the expression of the signature in CSCs by quantitative RT-PCR. Results. mRNAsi was significantly elevated in tumor and high-mRNAsi score was associated with poor overall survival in HCC. The positive stemness-associated (blue) module with 737 genes were screened based on WGCNA, and Budding uninhibited by benzimidazoles 1 (BUB1) was identified as the hub gene highly related to stemness in HCC. Then, the prognostic value and stemness characteristics were well validated in the ICGC and GSE14520 cohorts. Further analysis showed the expression of BUB1 was elevated in TRCs. Conclusion. BUB1, as a potential stemness-associated biomarker, could serve as a therapeutic CSCs-target and predicted the clinical outcomes of patients with HCC.http://dx.doi.org/10.1155/2022/1534593 |
| spellingShingle | Yangyang Zhang Ruike Zhang Lingxiu Zeng Haizhou Wang Ruyi Peng Meng Zhang Hailin Zhang Zhenwei Yang Liping Gao Meng Wang Jing Liu Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma Stem Cells International |
| title | Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma |
| title_full | Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma |
| title_fullStr | Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma |
| title_full_unstemmed | Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma |
| title_short | Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma |
| title_sort | identification and validation of a potential stemness associated biomarker in hepatocellular carcinoma |
| url | http://dx.doi.org/10.1155/2022/1534593 |
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