# ARIH2 serves as a potential prognostic biomarker for hepatocellular carcinoma associated with immune infiltration and ferroptosis

**Authors:** Qiang Shu, Qiang Wang, Xiaoli Yang, Bo Li

PMC · DOI: 10.3389/fimmu.2025.1548691 · Frontiers in Immunology · 2025-04-07

## TL;DR

This study identifies ARIH2 as a potential biomarker for predicting the prognosis of hepatocellular carcinoma, linking it to immune infiltration and ferroptosis.

## Contribution

The novel contribution is identifying ARIH2 as a prognostic biomarker for HCC associated with immune infiltration and ferroptosis.

## Key findings

- ARIH2 is upregulated in HCC tumor tissues compared to normal liver tissues.
- ARIH2 expression correlates with immune infiltration, immune checkpoint genes, and ferroptosis in HCC.
- ARIH2 expression independently predicts overall survival and clinical characteristics in HCC patients.

## Abstract

Ariadne homolog 2 (ARIH2) has been demonstrated to be upregulated in various human cancer tissues. Nevertheless, the underlying biological function of ARIH2 in the progression of hepatocellular carcinoma (HCC) remains ambiguous. Hence, we conducted a comprehensive bioinformatics analysis on the liver hepatocellular carcinoma (LIHC) dataset to explore the role of ARIH2 in tumorigenesis.

The mRNA and protein expression of ARIH2 was analyzed by using data from public databases and verified through immunohistochemical staining and Western blot. Logistic regression, Cox regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis and nomogram model were employed to assess the association between ARIH2 and the clinicopathological characteristics of HCC. We utilized functional enrichment analysis to investigate the potential pathways of ARIH2 in the progression of HCC. The association of ARIH2 with immune infiltration, ferroptosis and immune checkpoint genes was further evaluated. Finally, the correlation between ARIH2 and the IC50 of chemotherapeutic drugs was analyzed in HCC.

Our study discovered that ARIH2 was up-regulated in HCC tumor tissues compared with the control group. ARIH2 expression could effectively distinguish tumor tissues from normal liver tissues. The genes related to ARIH2 showed differential expression in pathways involving immune system-related pathways and ion channels. We identified a significant association between the expression level of ARIH2 in HCC tissues and immune infiltration, immune checkpoint genes and ferroptosis. The expression level of ARIH2 was significantly correlated with the clinical stage, histological pathological grade and clinical characteristics of HCC, and could independently predict overall survival.

The expression level of ARIH2 may serve as a promising biomarker for the diagnosis and prognosis of HCC, as well as a potential drug target, which holds great significance for the development of targeted therapy for HCC.

## Linked entities

- **Genes:** ARIH2 (ariadne RBR E3 ubiquitin protein ligase 2) [NCBI Gene 10425]
- **Diseases:** hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)

## Full-text entities

- **Genes:** ARIH2 (ariadne RBR E3 ubiquitin protein ligase 2) [NCBI Gene 10425] {aka ARI2, TRIAD1}
- **Diseases:** tumorigenesis (MESH:D063646), cancer (MESH:D009369), HCC (MESH:D006528)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12009847/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12009847/full.md

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Source: https://tomesphere.com/paper/PMC12009847