Identification of SCAF1 as a key factor affecting VEGF in LIHC and its potential target for therapy hypothesized based on network pharmacology and transcriptomics

Abstract

Abstract Introduction: Liver hepatocellular carcinoma (LIHC) is a highly vascularized entity closely associated with immune functions, characterized by high incidence, elusive early detection, high malignancy, and poor prognosis. SCAF1 participates in the immune regulation mechanisms of various cancers (gliomas, breast cancer, etc.) and is involved in regulating the level of gene transcription. Nevertheless, there is currently no research focusing on the multiple mechanisms of SCAF1 in LIHC, including angiogenesis promotion and immunomodulation.Materials and Methods: In this study, we obtained TCGA data and utilized Weighted Gene Co-expression Network Analysis (WGCNA) to explore hub genes, followed by evaluating the prognostic and clinical significance of SCAF1. Functional identification of SCAF1 in LIHC was performed through enrichment analysis. Subsequently, the immune therapeutic effects of SCAF1 were explored using TIMER and TISIDB. Spatial transcriptomics and single-cell sequencing analysis based on GEO data were conducted to assess heterogeneity tissue within the tumor microenvironment. Finally, molecular docking predictions were performed using Perl to evaluate pharmacological effects.Results: We identified a significant upregulation of SCAF1 in LIHC, and its overexpression may lead to decreased patient survival rates, enhanced levels of angiogenesis, invasion, and migration capabilities in LIHC. Chemokine analysis results demonstrated that the up-regulation of SCAF1 expression could inhibit the expression of cell factors such as CCL19. Experimental results demonstrated that genistein could downregulate SCAF1 and VEGFA in LIHC and inhibit cell invasion and migration levels.Conclusion: SCAF1 can influence angiogenesis in LIHC and affect tumor progression and therapeutic outcomes in LIHC patients through angiogenesis regulation.