# Multidimensional analysis suggests that ZNF433 is a promising biomarker for the diagnosis and prognosis of human cancers

**Authors:** Lingyu Xie, Xin Zeng, Hui Luo, Bin Xie, Xuefeng Wang, Nan Wu, Junrong Zou, Guoxi Zhang, Xiaofeng Zou, Hui Xu

PMC · DOI: 10.3389/fonc.2025.1584042 · Frontiers in Oncology · 2025-06-25

## TL;DR

ZNF433 shows promise as a cancer diagnostic and prognostic biomarker, with varied expression and survival associations across different cancer types.

## Contribution

This study is the first to comprehensively analyze ZNF433's role in cancer using multi-dimensional data from public databases.

## Key findings

- ZNF433 is significantly downregulated in most cancers and shows stage-dependent expression in KIRC and KIRP.
- High ZNF433 expression correlates with improved survival in some cancers but poorer outcomes in others.
- ZNF433 is linked to genomic instability markers and has diagnostic potential in LAML and TGCT.

## Abstract

Zinc finger proteins, particularly members of the Krüppel-associated box zinc finger proteins (KRAB-ZFPs), play critical roles in regulating gene expression, cell cycle progression, and epigenetic modifications. Despite the growing body of research on KRAB-ZFPs, the role of ZNF433, a relatively less studied member of this family, remains poorly understood in the context of cancer.

We conducted multi-dimensional analyses using publicly available databases, including TCGA and GTEx, to evaluate ZNF433’s expression patterns, genetic mutations, survival outcomes, immune microenvironment interactions, and diagnostic potential across different cancers. Functional enrichment and protein interaction network analyses were also performed to explore its potential involvement in cancer-related pathways.

Our findings revealed that ZNF433 is significantly downregulated in most cancer types, with stage-dependent expression patterns observed in KIRC and KIRP. High expression of ZNF433 was associated with improved overall survival (OS) in HNSC and KIRC, while in ESCA and PRAD, it was correlated with poorer disease-free survival (DFS). Additionally, high ZNF433 levels were linked to better DFS in BRCA, KIRP, THYM, and KIRC. ZNF433 expression was also closely associated with genomic instability markers, including tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) deficiencies. Furthermore, ZNF433 exhibited significant regulatory roles within the tumor immune microenvironment. Diagnostic analysis showed that ZNF433 has strong diagnostic potential in LAML and TGCT, and moderate diagnostic value in other cancers.

Our study highlights the potential of ZNF433 as a diagnostic and prognostic biomarker and provides new insights into its potential as a therapeutic target.

## Linked entities

- **Genes:** ZNF433 (zinc finger protein 433) [NCBI Gene 163059]
- **Diseases:** cancer (MONDO:0004992), PRAD (MONDO:0005082), BRCA (MONDO:0006256), THYM (MONDO:0006456), TGCT (MONDO:0010108)

## Full-text entities

- **Genes:** BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, ZNF433 (zinc finger protein 433) [NCBI Gene 163059]
- **Diseases:** cancer (MESH:D009369), TGCT (MESH:C563236)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12237650/full.md

## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC12237650/full.md

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Source: https://tomesphere.com/paper/PMC12237650