Radiogenomic correlation of hypoxia-related biomarkers in clear cell renal cell carcinoma

This study aimed to evaluate radiomic models' ability to predict hypoxia-related biomarker expression in clear cell renal cell carcinoma (ccRCC).

Clinical and molecular data from 190 patients were extracted from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma dataset, and corresponding CT imaging data were manually segmented from The Cancer Imaging Archive. A panel of 2,824 radiomic features was analyzed, and robust, high-interscanner-reproducibility features were selected. Gene expression data for 13 hypoxia-related biomarkers were stratified by tumor grade (1/2 vs. 3/4) and stage (I/II vs. III/IV) and analyzed using Wilcoxon rank sum test. Machine learning modeling was conducted using the High-Performance Random Forest (RF) procedure in SAS Enterprise Miner 15.1, with significance at P < 0.05.

Descriptive univariate analysis revealed significantly lower expression of several biomarkers in high-grade and late-stage tumors, with KLF6 showing the most notable decrease. The RF model effectively predicted the expression of KLF6, ETS1, and BCL2, as well as PLOD2 and PPARGC1A underexpression. Stratified performance assessment showed improved predictive ability for RORA, BCL2, and KLF6 in high-grade tumors and for ETS1 across grades, with no significant performance difference across grade or stage.

The RF model demonstrated modest but significant associations between texture metrics derived from clinical CT scans, such as GLDM and GLCM, and key hypoxia-related biomarkers including KLF6, BCL2, ETS1, and PLOD2. These findings suggest that radiomic analysis could support ccRCC risk stratification and personalized treatment planning by providing non-invasive insights into tumor biology.