# Elevated DOCK4 expression correlates with favorable prognosis and immune infiltration in clear cell renal cell carcinoma

**Authors:** Da-Long He, Fang-Fang Zhu, Jia Wang, Su-Wei Zhu, Shao-Shuai Hou

PMC · DOI: 10.1080/07853890.2026.2642533 · Annals of Medicine · 2026-03-13

## TL;DR

High DOCK4 levels in kidney cancer are linked to better survival and stronger immune response, suggesting it could help guide treatment.

## Contribution

DOCK4 is identified as a novel prognostic biomarker and potential immunotherapy target in clear cell renal cell carcinoma.

## Key findings

- High DOCK4 expression correlates with favorable pathologic staging and improved survival in ccRCC.
- DOCK4 shows strong discriminatory power between tumor and normal tissues with an AUC of 0.819.
- DOCK4 is associated with immune infiltration, suggesting a role in enhancing immunotherapy response.

## Abstract

Clear-cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer, has limited treatment options. This study investigated the expression and clinical significance of DOCK4 in ccRCC, hypothesizing that DOCK4 could serve as a prognostic biomarker and correlate with the tumor immune microenvironment (TIME) and immunotherapy response.

We comprehensively analyzed data on DOCK4 expression levels and prognostic outcomes in ccRCC patients derived from tissue microarray (75 pairs) and the dataset (532 cases). Based on univariate and multivariate Cox regression analyses, we constructed a prognostic nomogram and validated its predictive accuracy and risk stratification ability using calibration curves and Kaplan‑Meier survival analysis. Immune cell infiltration analysis was conducted to investigate DOCK4’s role in the TIME.

Analysis of DOCK4 expression in ccRCC tissues revealed its notable overexpression. High DOCK4 expression was associated with more favorable pathologic staging and improved survival outcomes. DOCK4 shows high discriminatory power between tumor and normal samples, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.819. This association was confirmed using tissue microarray analysis. Further investigation indicated that high DOCK4 expression may play a crucial role in modulating the TIME, potentially enhancing susceptibility to immunotherapy and strengthening immune surveillance mechanisms.

DOCK4 is a promising prognostic biomarker in ccRCC, with high expression indicating favorable pathologic staging and improved survival. Its role in modulating the TIME suggests that DOCK4 could also serve as a therapeutic target, potentially guiding future immunotherapy strategies for this aggressive malignancy.

This study integrates microarray and multiple database results to demonstrate that DOCK4 serves as a prognostic biomarker for clear cell renal cell carcinoma (ccRCC) and suggests its potential as a basis for guiding immunotherapy sensitivity assessment.

## Linked entities

- **Genes:** DOCK4 (dedicator of cytokinesis 4) [NCBI Gene 9732]
- **Diseases:** clear cell renal cell carcinoma (MONDO:0005005), ccRCC (MONDO:0007763)

## Full-text entities

- **Genes:** DOCK4 (dedicator of cytokinesis 4) [NCBI Gene 9732]
- **Diseases:** kidney cancer (MESH:D007680), malignancy (MESH:D009369), Clear-cell renal cell carcinoma (MESH:D002292)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12990261/full.md

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Source: https://tomesphere.com/paper/PMC12990261