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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.