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Published on: October 24, 2016
Exploring the role of CDCA4 in liver hepatocellular carcinoma using bioinformatics analysis and experiments
Changfu Liang1, Kaijun Long, Wenhao Zheng
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Hainan Medical College, Haikou, China.
Abstract:
Liver hepatocellular carcinoma (LIHC) encompasses diverse therapeutic approaches, among which targeted therapy has gained significant prominence in recent years. The identification of numerous targets and the increasing clinical application of targeted drugs have greatly improved LIHC treatment. However, the precise role of CDCA4 (Cell Division Cycle Associated 4), as well as its underlying mechanisms and prognostic implications in LIHC, remains unclear. CDCA4 expression levels in LIHC were analyzed using multiple databases including the cancer genome atlas (TCGA), gene expression profiling interactive analysis (GEPIA), and ULCAN, as well as the datasets E_TABM_36, GSE144269, GSE14520, and GSE54236. The prognostic value of CDCA4 was then evaluated. Subsequently, the association between CDCA4 and immune cells was investigated. Enrichment analysis (GSEA) was utilized to investigate the functional roles and pathways linked to CDCA4. Additionally, the methylation patterns and drug sensitivity of CDCA4 were examined. A predictive model incorporating immune genes related to CDCA4 was developed. The TISCH dataset was used to investigate the single-cell expression patterns of CDCA4. Finally, validation of CDCA4 expression levels was conducted through RT-PCR, Western blotting, and immunohistochemistry. CDCA4 exhibited significant overexpression in LIHC and demonstrated significant correlations with clinical features. High expression of CDCA4 is associated with a poorer prognosis. Analysis of immune infiltration and enrichment revealed its association with the immune microenvironment. Furthermore, its expression is correlated with methylation and mutation patterns. CDCA4 is associated with 19 drugs. Prognostic models utilizing CDCA4 demonstrate favorable effectiveness. T cell subtypes were found to be associated with CDCA4 through single-cell analysis. The conclusive experiment provided evidence of significant upregulation of CDCA4 in LIHC. The high expression of CDCA4 in LIHC is associated with prognostic significance and is highly expressed in T cell subtypes, providing a new therapeutic target and potential therapeutic strategy for LIHC.
Insights
Cell Division Cycle Associated 4 (CDCA4) is overexpressed in liver hepatocellular carcinoma (LIHC), correlating with poor prognosis and immune microenvironment changes. This study identifies CDCA4 as a potential therapeutic target for LIHC.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Liver hepatocellular carcinoma (LIHC) treatment is advancing with targeted therapies.
- The role and prognostic significance of Cell Division Cycle Associated 4 (CDCA4) in LIHC are not well understood.
- Clarifying CDCA4's function is crucial for developing novel LIHC therapeutic strategies.
Purpose of the Study:
- To investigate the expression levels, prognostic value, and underlying mechanisms of CDCA4 in LIHC.
- To explore the association between CDCA4 and the tumor immune microenvironment.
- To evaluate CDCA4's potential as a therapeutic target and biomarker in LIHC.
Main Methods:
- Analysis of CDCA4 expression using multiple public databases (TCGA, GEPIA, ULCAN, E_TABM_36, GSE series).
- Prognostic value assessment, immune cell infiltration analysis, and Gene Set Enrichment Analysis (GSEA).
- Investigation of methylation, drug sensitivity, single-cell expression (TISCH), and experimental validation (RT-PCR, Western blot, IHC).
Main Results:
- CDCA4 was significantly overexpressed in LIHC tissues and correlated with clinical features and poorer prognosis.
- CDCA4 expression is linked to the immune microenvironment, methylation patterns, and drug sensitivity (19 drugs identified).
- Single-cell analysis revealed CDCA4 expression in T cell subtypes; prognostic models showed effectiveness.
Conclusions:
- High CDCA4 expression in LIHC is associated with adverse prognosis and immune cell infiltration.
- CDCA4 represents a potential biomarker and therapeutic target for LIHC.
- Further research into CDCA4-targeting strategies may improve LIHC treatment outcomes.
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