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Background: Radiogenomics integrates imaging features with genomic data to improve biological understanding and support personalized risk stratification in oncology. Clear cell renal cell carcinoma (ccRCC) exhibits substantial molecular and radiological heterogeneity. Chromobox 4 (CBX4), a polycomb group protein with known oncogenic activity, has been implicated in promoting tumor proliferation, migration, and adverse outcomes in ccRCC. However, its potential radiogenomic signature has not been previously characterized. The purpose of this article is to evaluate whether CBX4 expression correlates with computed tomography (CT) features associated with aggressive tumor behavior in ccRCC. Methods: CBX4 expression was extracted from The Cancer Genome Atlas (TCGA) RNA-sequencing data. Clinical characteristics and CT features (such as tumor size, margin definition, growth pattern, infiltration, and collateral vascular supply) were collected. Data collection and download were performed on November 1, 2019, and data collection continued for the following five months. Patients were identified from the TCGA-Kidney Renal Clear Cell Carcinoma (KIRC) project according to predefined inclusion and exclusion criteria. Inclusion criteria comprised a histological diagnosis of ccRCC, availability of pre-treatment contrast-enhanced CT scans, and corresponding RNA-sequencing data within the TCGA-KIRC database. Individuals were excluded if imaging data were missing or of inadequate quality, or if matched gene expression data were unavailable. The final study cohort consisted of 206 patients who fulfilled all eligibility requirements. Associations were assessed using Wilcoxon rank-sum, Chi-square, and Fisher’s exact tests. Results: Among 206 ccRCC patients included in this cross-sectional study (42.2% CBX4-positive), CBX4 expression was associated with larger tumors (P=0.002), higher grade (P=0.04), advanced stage (P=0.02), ill-defined margins (P=0.01), ≥50% exophytic growth (P=0.03), collateral vascular supply (P=0.03), and infiltration (P=0.01). Conclusions: CBX4 expression is associated with CT features indicative of more aggressive ccRCC. These results suggest that CBX4 may serve as a radiogenomic marker with potential relevance for non-invasive prognostic stratification. Further prospective studies with standardized imaging protocols and experimental validation are needed to confirm these associations and to clarify the role of CBX4 within precision-oncology pathways.