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Published online: 2024-06-11

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ARPC3 affects the prognosis for patients with hepatocellular carcinoma by regulating the immune response

Yonghu Song1, Jianhui Li1, Zhenyang Lu1, Yijun Qi1


Introduction. Actin related protein 2/3 complex subunit 3 (ARPC3) is associated with a poor prognosis in patients with various cancers. However, the mechanisms by which it affects immunotherapy and prognosis in patients with hepatocellular carcinoma (HCC) remain unclear. 

To explore the effect of ARPC3 on immune checkpoint inhibitors (ICIs), we investigated the association of ARPC3 with immunotherapy-associated ferroptosis genes. 

Material and methods. The expression difference in ARPC3 between normal and HCC tissues and the effect of ARPC3 on prognosis were evaluated by using multiple databases. GSEA was used to predict the pathway by which ARPC3 affects HCC progression. Using the TCGA database, the First Affiliated Hospital of Anhui Medical University (AHMU) database, and the ICGC database, the correlation between ARPC3, tumor-infiltrating lymphocytes (TILs) and immune checkpoints was studied. 

Results. The expression of ARPC3 in normal tissues was lower than that in tumor tissues, and as an independent prognostic risk factor for HCC, patients with HCC whose ARPC3 expression was high had a worse prognosis. GSEA suggested that the upregulation of ARPC3 mainly affected immune-related pathways. Three databases showed that ARPC3 expression levels affected the infiltration levels of B cells, T cells, macrophages, neutrophils, and NK cells in tumors. In addition, we confirmed that ARPC3 may influence the efficacy of ICI therapy by affecting the expression of immune checkpoints and ferroptosis-related genes in HCC. 

Conclusions. ARPC3 is an independent prognostic risk factor for HCC patients and may influence HCC immunotherapy by affecting the expression of immune checkpoints and ferroptosis-related genes.

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