Construction of a Liver Cancer Prognostic Model Based on Interferon-Gamma-Related Genes for Revealing the Immune Landscape.

Inferferon-gamma (LFN-γ) exerts anti-tumor effects, but there is currently no reliable and comprehensive study on prognostic function of IFN-γ-related genes in liver cancer. In this study, IFN-γ-related differentially expressed genes (DEGs) in liver cancer were identified through GO/KEGG databases and open-access literature. Based on these genes, individuals with liver cancer were clustered. A prognostic model was built based on the intersection genes between differential genes in clusters and in liver cancer. Then, model predictive performance was analyzed and validated in GEO dataset. Regression analysis was fulfilled on the model, and a nomogram was utilized to evaluate model ability as an independent prognostic factor and its clinical application value. An immune-related analysis was conducted on both the H- and L-groups, with an additional investigation into link of model genes to drug sensitivity. Significant differential expression of IFN-γ-related genes was observed between the liver cancer and control groups. Subsequently, individuals with liver cancer were classified into two subtypes based on these genes, which displayed a notable difference in survival between the two subtypes. A 10-gene liver cancer prognostic model was constructed, with good prognostic performance and was an independent prognosticator for patient analysis. L-group patients possessed higher immune infiltration levels, immune checkpoint expression levels, and immunophenoscore, as well as lower TIDE scores. Drugs that had high correlations with the feature genes included SPANXB1: PF-04217903, SGX-523, MMP1: PF-04217903, DUSP13: Imatinib, TFF1: KHK-Indazole, and Fulvestrant. We built a 10-gene liver cancer prognostic model. It was found that L-group patients were more suitable for immunotherapy. This study provided valuable information on the prognosis of liver cancer.

Comprehensively prognostic and immunological analysis of VRK Serine/Threonine Kinase 1 in pan-cancer and identification in hepatocellular carcinoma.

BACKGROUND: VRK1 is a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases, which is related to the occurrence and development of malignant tumors. The expression pattern, predictive value, and biological function of VRK1 in various cancers remain largely elusive and warrant further investigation. METHODS: Public databases, such as TCGA, GTEx, and UCEC, were utilized to comprehensively analyze the expression of VRK1 across multiple cancer types. Prognostic significance was assessed through Univariate Cox regression and Kaplan-Meier analyses. Additionally, Spearman's correlation analysis was employed to explore the potential associations between VRK1 expression and various factors, including tumor microenvironment scores, immune cell infiltration, and immune-related genes. Moreover, to validate the findings, differential expression of VRK1 in HCC tissues and cell lines was further confirmed using qPCR, Western blot, and immunohistochemistry techniques. RESULTS: The upregulation of VRK1 was observed in most cancer types, and was associated with worse prognosis in ACC, KICH, KIRP, LGG, LIHC, LUAD, MESO, and PCPG. In various cancers, VRK1 expression exhibited positive correlations with immune infiltrating cells, immune checkpoint-related genes, TMB, and MSI. Furthermore, the promoter methylation status of VRK1 varied across different tumor types, and this variation was associated with patient prognosis in certain cancers. In our experimental analyses, we observed significantly elevated expression of VRK1 in both HCC tissues and HCC cells. Functionally, we found that the downregulation of VRK1 had a profound impact on HCC cells, leading to a significant decrease in their proliferation, migration, and invasion capabilities. CONCLUSION: The expression of VRK1 exerts a notable influence on the prognosis of several tumors and exhibits a strong correlation with tumor immune infiltration. Moreover, in the context of HCC, VRK1 may act as an oncogene, actively promoting tumor progression.