Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and it has an unfavourable prognosis compared to other RCCs. Plant homeodomain finger 2 (PHF2) and CCATT/enhancer binding protein α (C/EBPα) play a role in the epigenetic regulation of adipogenesis, and their tumour suppressive functions have been elucidated. This study aimed to assess the nuclear expression of PHF2 and C/EBPα in ccRCC and to evaluate their role in pathogenesis and prognosis. The nuclear expression of PHF2 and C/EBPα was evaluated in 344 cases of ccRCC by immunohistochemistry, and adipogenesis was assessed based on cytoplasmic features. Low expression was significantly associated with a larger tumour size, higher WHO/ISUP grade, high pT, pM, and advanced pTNM stage. Additionally, the expression level was correlated with the cytoplasmic features of ccRCC. The low expression group had significantly shorter cancer-specific and progression-free survival times. Furthermore, multivariate analysis showed that the combination of PHF2 and C/EBPα expression as an independent prognostic factor for cancer-specific and progression-free survival. In conclusion, our results suggest that nuclear expression of PHF2 and C/EBPα may serve as a prognostic marker and that the oncogenic metabolic shift has progressed in ccRCC patients.