A pathomics-based pyroptosis signature predicts survival in clear cell renal cell carcinoma

Better prognostic tools are needed to improve the clinical management of clear cell renal cell carcinoma (ccRCC). To address this, we developed a novel prognostic model by integrating pathomics features with pyroptosis-related signaling, a strategy not previously explored in ccRCC. Analysis of The Cancer Genome Atlas (TCGA) whole-slide images identified 59 quantitative image features significantly correlated with a pyroptosis gene set. Based on these features, a prognostic risk score was developed using the StepCox[forward]+Lasso algorithm and validated as an independent predictor of patient survival. This model demonstrated robust predictive performance, with time-dependent AUCs of 0.744, 0.729, and 0.716 for 1-, 3-, and 5-year survival and C-indexes of 0.71 and 0.64 in the training and validation sets. This model implicates key pyroptosis-related genes (e.g., GSDMD, GSDME, CASP5, and several CHMP family genes), whose expression links pathological phenotypes to patient outcomes. Single-cell sequencing revealed their specific expression patterns in the ccRCC microenvironment, and functional exploration highlighted GSDMD's potential role. By providing a novel, biologically integrated signature, this model offers a refined tool for prognostic assessment that complements conventional clinical parameters. Ultimately, this pyroptosis-based pathomics model could help guide personalized treatment strategies for ccRCC patients in the future.