Identification of clear cell renal cell carcinoma subtypes by integrating radiomics and transcriptomics.

Objective: This study aimed to delineate the clear cell renal cell carcinoma (ccRCC) intrinsic subtypes through unsupervised clustering of radiomics and transcriptomics data and to evaluate their associations with clinicopathological features, prognosis, and molecular characteristics. Methods: Using a retrospective dual-center approach, we gathered transcriptomic and clinical data from ccRCC patients registered in The Cancer Genome Atlas and contrast-enhanced computed tomography images from The Cancer Imaging Archive and local databases. Following the segmentation of images, radiomics feature extraction, and feature preprocessing, we performed unsupervised clustering based on the "CancerSubtypes" package to identify distinct radiotranscriptomic subtypes, which were then correlated with clinical-pathological, prognostic, immune, and molecular characteristics. Results: Clustering identified three subtypes, C1, C2, and C3, each of which displayed unique clinicopathological, prognostic, immune, and molecular distinctions. Notably, subtypes C1 and C3 were associated with poorer survival outcomes than subtype C2. Pathway analysis highlighted immune pathway activation in C1 and metabolic pathway prominence in C2. Gene mutation analysis identified VHL and PBRM1 as the most commonly mutated genes, with more mutated genes observed in the C3 subtype. Despite similar tumor mutation burdens, microsatellite instability, and RNA interference across subtypes, C1 and C3 demonstrated greater tumor immune dysfunction and rejection. In the validation cohort, the various subtypes showed comparable results in terms of clinicopathological features and prognosis to those observed in the training cohort, thus confirming the efficacy of our algorithm. Conclusion: Unsupervised clustering based on radiotranscriptomics can identify the intrinsic subtypes of ccRCC, and radiotranscriptomic subtypes can characterize the prognosis and molecular features of tumors, enabling noninvasive tumor risk stratification.