Comprehensive pan-cancer analysis reveals CD70 as a promising therapeutic target and biomarker in clear cell renal cell carcinoma

CD70, a member of the tumor necrosis factor family, has been implicated in various cellular processes associated with tumorigenesis. Despite its known expression in certain cancers, a detailed pan-cancer analysis and functional validation in clear cell renal cell carcinoma (ccRCC) have not been comprehensively explored. We conducted a pan-cancer analysis using publicly available databases to investigate the expression and prognostic significance of CD70 across various cancer types. For functional validation, immunohistochemistry was performed on ccRCC and adjacent normal tissues to evaluate CD70 expression levels. Additionally, ccRCC organoid model was developed and subjected to CAR-T cell cytotoxicity assays to evaluate the efficacy of targeting CD70 in vitro. The pan-cancer analysis revealed elevated expression of CD70 in several cancer types, including ccRCC, where it correlated with poor prognosis. Immunohistochemical analysis confirmed significant overexpression of CD70 in ccRCC tissues compared to normal tissues. In the ccRCC organoid model, CAR-T cells targeting CD70 demonstrated effective cytotoxicity against organoids expressing CD70. The overexpression of CD70 across diverse cancer types underscores its potential as a universal biomarker. Importantly, our findings underscore the clinical relevance of CD70 as a critical oncogenic factor and a promising therapeutic target in ccRCC, with implications for advancing personalized medicine.