Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis

Tao, Haisu; Li, Jiang; Liu, Junjie; Yuan, Tong; Zhang, Erlei; Liang, Huifang; Huang, Zhiyong

doi:10.7150/jca.57260

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J Cancer 2021; 12(13):3754-3768. doi:10.7150/jca.57260 This issue Cite

Research Paper

Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis

Haisu Tao^1,2, Jiang Li^1,2, Junjie Liu^1,2, Tong Yuan^1,2, Erlei Zhang^1,2, Huifang Liang^1,2, Zhiyong Huang^1,2✉

1. Hepatic Surgery Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
2. Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, China.

Citation:

Tao H, Li J, Liu J, Yuan T, Zhang E, Liang H, Huang Z. Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis. J Cancer 2021; 12(13):3754-3768. doi:10.7150/jca.57260. https://www.jcancer.org/v12p3754.htm

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Abstract

Background: Understanding risk factors for vascular invasion (VI) is crucial for assessing the risk of recurrence and overall prognosis of hepatocellular carcinoma (HCC). This study aimed to construct a prognostic long non-coding RNA (lncRNA) signature and a ceRNA Network associated with vascular invasion in HCC.

Methods: Differentially expressed genes (DEGs) of HCC patients associated with VI were identified by analyzing data from TCGA. Weighted gene co-expression network analysis (WGCNA) was used to identify associations between gene expression modules and clinical features. A VI-related prognostic lncRNA signature was then established using univariate, LASSO and multivariate Cox proportional hazards regression analyses. Based on the hub modules identified by the WGCNA, we constructed a VI-related lncRNA-miRNA-mRNA ceRNA network and screened hub lncRNAs for further research. Finally, we conducted in vitro and in vivo experiments to determine the biological roles of the identified hub gene BBOX1-AS1.

Results: The key module related to VI and OS was identified using WGCNA, after which a prognostic model consisting of eight lncRNAs was established, and verified using time-dependent receiver operating characteristic (ROC) curve analysis. BBOX1-AS1 was confirmed to be highly expressed in HCC tissues, and its expression was significantly correlated with a poor prognosis. Silencing BBOX1-AS1 in vitro significantly suppressed the proliferation, migration and invasion of HCC cells. In vivo experiments demonstrated that knocking down of BBOX1-AS1 could result in significant decrease of tumor volume and tumor weight.

Conclusions: The VI-related lncRNA signature established in this study can be used to predict the clinical outcomes of HCC patients. In addition, we constructed a VI-related lncRNA-miRNA-mRNA ceRNA network and demonstrated that BBOX1-AS1 might be a novel biomarker associated with VI in HCC.

Keywords: HCC, vascular invasion, ceRNA, prognostic signature, BBOX1-AS1

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APA

Tao, H., Li, J., Liu, J., Yuan, T., Zhang, E., Liang, H., Huang, Z. (2021). Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis. Journal of Cancer, 12(13), 3754-3768. https://doi.org/10.7150/jca.57260.

ACS

Tao, H.; Li, J.; Liu, J.; Yuan, T.; Zhang, E.; Liang, H.; Huang, Z. Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis. J. Cancer 2021, 12 (13), 3754-3768. DOI: 10.7150/jca.57260.

NLM

CSE

Tao H, Li J, Liu J, Yuan T, Zhang E, Liang H, Huang Z. 2021. Construction of a ceRNA Network and a Prognostic lncRNA Signature associated with Vascular Invasion in Hepatocellular Carcinoma based on Weighted Gene Co-Expression Network Analysis. J Cancer. 12(13):3754-3768.

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