Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, which is characterized by transparent cytoplasm. However, some ccRCC also show eosinophilic cytoplasm, and the molecular difference between eosinophilic and clear subtypes is unclear. In this study, we uncovered that under an optical microscope ccRCC with eosinophilic features has a poor prognosis. Eosinophilic ccRCC tends to have a higher histologic grade. Eosinophilic ccRCC has 16 genes significantly up-regulated compared with ccRCC, of which seven genes have multi-cohort validation prognostic value. Immune infiltration analysis suggested a low number of M1 macrophages and NK tissue-resident cells in eosinophilic ccRCC. Enrichment analysis suggests that ccRCC with eosinophilic features may be closely associated with the transport and metabolism of many substances. The findings of this study have important implications for the study of the malignant transformation of ccRCC.