Objective:

To characterize the oncogenic role of CACUL1 in hepatocellular carcinoma (HCC) and its impact on tumor growth and immune suppression.

Approach:

• Pan-cancer analysis: Utilized TCGA and GEO databases for expression and survival analysis, validated findings through immunohistochemistry.
• Functional studies: Conducted CRISPR-mediated CACUL1 knockout in HCC cell lines, followed by transcriptome sequencing and functional assays.
• Co-culture experiments: Investigated the effect of CACUL1 on macrophage polarization and immune response.

Key Findings:

• CACUL1 is overexpressed in HCC and gastric cancer, with prognostic significance in 16 tumor types.
• CACUL1 expression independently predicts poor prognosis in HCC.
• CACUL1 knockout inhibits HCC cell proliferation and migration, linked to PI3K/AKT signaling pathway enrichment.
• CACUL1 promotes M2 macrophage polarization through Notch1 suppression.

Interpretation:

Limitations:

• The study primarily focuses on in vitro and in vivo models, which may not fully replicate human disease complexity.
• Further clinical validation is needed to confirm CACUL1 as a prognostic biomarker.

Conclusion:

CACUL1 is identified as a potential prognostic biomarker in hepatocellular carcinoma.