Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma

Purpose Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism–related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism–related proteins on patient prognoses in advanced stage ccRCCs. Materials and Methods All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation. Results FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival. Conclusion FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.