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Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
Published on: August 18, 2023
Identification of oncogenes and tumor-suppressor genes with hepatocellular carcinoma: A comprehensive analysis based
Yue Zhu1, Yanfei Wang1,2, Mengyao Hu1,2
1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Abstract:
Aim: Existing targeted therapies for hepatocellular carcinoma (HCC) are resistant and have limitations. It is crucial to find new HCC-related target genes. Methods: RNA-sequencing data of HCC were gathered from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Initially, differentially expressed genes between normal and tumor tissues were identified from four Gene Expression Omnibus datasets, GSE36376, GSE102079, GSE54236, and GSE45267. GO terms and KEGG pathway enrichment analyses were performed to explore the potential biological functions of differentially expressed genes. A PPI network was constructed by using the STRING database, and up-regulated and down-regulated hub genes were defined through 12 topological approaches. Subsequently, the correlation bounded by up-regulated genes and down-regulated genes in the diagnosis, prognosis, and clinicopathological features of HCC was analyzed. Beyond a shadow of doubt, the key oncogene PBK and tumor suppressor gene F9 were screened out, and the specific mechanism was investigated through GSEA enrichment analysis and immune correlation analysis. The role of PBK in HCC was further verified by western blot, CCK8, transwell, and tube formation experiments. Results: CDCA5, CDC20, PBK, PRC1, TOP2A, and NCAPG are good indicators of HCC diagnosis and prognosis. The low expressions of F9, AFM, and C8B indicate malignant progression and poor prognosis of HCC. PBK was found to be closely related to VEGF, VEGFR, and PDGFR pathways. Experiments showed that PBK promotes HCC cell proliferation, migration, invasion, and tube formation in HUVEC cells. F9 was negatively correlated with the degree of immune infiltration, and low expression of F9 suggested a poor response to immunotherapy. Conclusion: The role of HCC-related oncogenes and tumor-suppressor genes in diagnosis and prognosis was identified. In addition, we have found that PBK may promote tumor proliferation through angiogenesis and F9 may be a predictor of tumor immunotherapy response.
Insights
New research identifies key genes, PBK and F9, for hepatocellular carcinoma (HCC) diagnosis and prognosis. PBK promotes tumor growth, while F9 may predict immunotherapy response in HCC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) treatments face resistance and limitations.
- Identifying novel HCC-associated target genes is crucial for developing effective therapies.
Purpose of the Study:
- To identify and characterize novel oncogenes and tumor suppressor genes in HCC.
- To investigate the diagnostic and prognostic roles of these genes.
- To explore the underlying mechanisms of PBK and F9 in HCC progression and treatment response.
Main Methods:
- RNA-sequencing data from TCGA and GEO datasets were analyzed to identify differentially expressed genes.
- Gene Ontology (GO) and KEGG pathway enrichment analyses were performed.
- Protein-protein interaction (PPI) network construction and topological analyses identified hub genes.
- Correlation analyses examined gene associations with HCC diagnosis, prognosis, and clinicopathological features.
- Gene Set Enrichment Analysis (GSEA) and immune correlation analysis elucidated specific mechanisms.
- Experimental validation included Western blot, CCK8, Transwell, and tube formation assays.
Main Results:
- Genes including CDCA5, CDC20, PBK, PRC1, TOP2A, and NCAPG are significant indicators for HCC diagnosis and prognosis.
- Low expression of F9, AFM, and C8B correlates with malignant progression and poor HCC prognosis.
- The oncogene PBK promotes HCC cell proliferation, migration, invasion, and angiogenesis, closely linked to VEGF, VEGFR, and PDGFR pathways.
- The tumor suppressor gene F9 shows a negative correlation with immune infiltration and may predict poor response to immunotherapy.
Conclusions:
- PBK and F9 are identified as critical oncogene and tumor suppressor gene, respectively, with significant roles in HCC diagnosis and prognosis.
- PBK promotes HCC tumor proliferation via angiogenesis, suggesting potential therapeutic targeting.
- F9 serves as a potential biomarker for predicting immunotherapy response in HCC patients.
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