Comprehensive analysis of ASB3 as a prognostic biomarker in hepatocellular carcinoma

Transl Oncol. 2024 Jan:39:101816. doi: 10.1016/j.tranon.2023.101816. Epub 2023 Nov 3.

Abstract

Background: Some reports have indicated a high expression level of ASB3 in various cancers, but its role in hepatocellular carcinoma (HCC) remains elusive.

Methods: ASB3 levels and clinical features were obtained from the TCGA database. Meanwhile, the expression levels of ASB3 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Imunohistochemistry (IHC). ASB3-related downstream molecular analysis was carried out with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways linked to ASB3 expression were identified by means of gene set enrichment analysis (GSEA). Single-sample GSEA (ssGSEA) aided in conducting a correlation analysis of ASB3 with immune infiltration. Functional experiments were performed in HepG2 cells by using the small interfering RNA.

Results: ASB3 expression was remarkably higher in HCC tissues. Its remarkable precision in forecasting cancer suggests that ASB3 might serve as an unidentified diagnostic and prognostic indicator of HCC. Higher ASB3 expression led to worse overall survival (OS), particularly in various clinical subgroups of HCC. GO/KEGG analysis indicated that critical biological activities, such as the activation of complement systems and humoral immune response, could potentially underlie the progression of HCC. Furthermore, GSEA demonstrated enrichment of certain pathways, including the MAPK, IL17, and fibrinolysis pathways, in samples with elevated ASB3 levels. ASB3 exhibited a substantial association with T helper cells, dendritic cells (DCs), and central memory T (Tcm) cell infiltration level. Cell function experiments confirmed elevated ASB3 levels in HCC cell lines as opposed to hepatic epithelial cell lines. Moreover, the ability of HCC cells to proliferate and invade was remarkably reduced by ASB3 knockdown.

Conclusion: Summarize briefly, we found that ASB3 can be a promising biomarker in HCC.

Keywords: ASB3; Hepatocellular Carcinoma; Immune infiltrate; Migration; Prognosis; Proliferation.