Radiogenomic Characterization of PHF2 Expression in Clear Cell Renal Cell Carcinoma: Associations with CT Phenotype and Lipid-Related Imaging Features

Plant homeodomain finger 2 (PHF2) is a histone demethylase involved in epigenetic regulation, tumor suppression, and adipogenic differentiation. Reduced PHF2 expression has been associated with adverse clinicopathological features in clear cell renal cell carcinoma (ccRCC). This study investigated whether PHF2 expression is associated with CT-derived phenotypic characteristics and imaging biomarkers potentially related to lipid metabolism in ccRCC. Clinical, pathological, transcriptomic, and CT imaging data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and The Cancer Imaging Archive (TCIA) were retrospectively matched. Patients were categorized into high- and low-PHF2-expression groups. Morphological CT features, unenhanced tumor attenuation, and abdominal total, visceral, and subcutaneous adipose tissue were assessed. Associations with PHF2 expression and correlations between tumor size and lipid-related imaging parameters were analyzed. A total of 205 patients were included (99 PHF2-high and 106 PHF2-low). Tumors with low PHF2 expression were significantly larger than those with high expression (67.1 ± 32.0 vs. 58.5 ± 30.3 mm, p = 0.031). No significant differences were observed in other clinicopathological or CT features, adipose tissue compartments, or tumor attenuation according to PHF2 expression. Tumor size correlated positively with mean (ρ = 0.301, p = 0.00007) and minimum (ρ = 0.174, p = 0.024) unenhanced CT attenuation. PHF2-low tumors were larger in the unadjusted analysis, although this association was not statistically significant after adjustment for clinicopathological factors. The association between increasing tumor size and higher unenhanced CT attenuation may reflect changes in tumor composition, potentially related to intracellular lipid content, during ccRCC growth.