Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma

作者：Yangyang Zhang, Ruike Zhang, Lingxiu Zeng, Haizhou Wang, Ruyi Peng, Meng Zhang, Hailin Zhang, Zhenwei Yang, Liping Gao, Meng Wang, Jing Liu · 发表于：Stem Cells International · 年份：2022 · DOI：10.1155/2022/1534593 · 被引用次数：3 · 研究领域：Cancer Cells and Metastasis、Ferroptosis and cancer prognosis、Hippo pathway signaling and YAP/TAZ

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 anal...