Identification of oncogenes and tumor-suppressor genes with hepatocellular carcinoma: A comprehensive analysis based on TCGA and GEO datasets

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.

Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas

“…Through consulting the literature , we were particularly interested in PBK, which is overexpressed in several human malignancies 20–24 . By analyzing the amino acid sequence of PBK, we found that PBK at Thr9 may be the potential phosphorylation site of CDK5.…”

“…Through consulting the literature, we were particularly interested in PBK, which is overexpressed in several human malignancies. [20][21][22][23][24] By analyzing the amino acid sequence of PBK, we found that PBK at Thr9 may be the potential phosphorylation site of CDK5. To further verify that CDK5 phosphorylates PBK-T9, HEK293 cells were transfected with GFP-CDK5 and FLAG-PBK.…”

Immunotherapy and drug sensitivity predictive roles of a novel prognostic model in hepatocellular carcinoma

“…Moreover, FBP1 appears to be a tumor suppressor in HCC progression though negatively regulating the Warburg effect 39 . In addition, studies have demonstrated that the expression of solute carrier family 22 member 1 (SLC22A1), alcohol dehydrogenase 4 (ADH4), solute carrier family 10 member 1 (SLC10A1), and coagulation factor IX (F9) was related to the progression and survival of HCC 6,[40][41][42] . However, there is no reference regarding the integration of these genes for the prognosis of patients with HCC.…”