Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Division of Hemato-Oncology, National Health Insurance Service (NHIS) Ilsan Hospital, Goyang, Korea.
Cancer Res Treat. 2021 Oct;53(4):1174-1183. doi: 10.4143/crt.2021.031. Epub 2021 Mar 17.
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.
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.
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.
FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.
晚期透明细胞肾细胞癌（ccRCC）预后较差。多项研究表明，铁代谢相关蛋白功能障碍可能导致该癌的肿瘤进展和转移。本研究旨在探讨铁代谢相关蛋白的表达对晚期 ccRCC 患者预后的影响。
采用双盲验证法选取 143 例晚期 ccRCC 标本。通过免疫组织化学方法比较核分级、肾周脂肪浸润、肾窦脂肪浸润、血管浸润、坏死和肉瘤样/横纹肌样分化等几种临床病理参数与铁输出蛋白（FPN）和 F 框和亮氨酸丰富重复蛋白 5（FBXL5）的表达。还分析了癌症基因组图谱数据库中 ccRCC 的 FPN 和 FBXL5 mRNA 水平以进行验证。
FPN 和 FBXL5 免疫组化分别显示膜和细胞质表达。根据 H 评分，病例分为低表达或高表达，FPN 的截断值为 20，FBXL5 的截断值为 15。FPN 和 FBXL5 低表达与患者死亡显著相关（p=0.022 和 p=0.005）。生存分析显示，FPN 和 FBXL5 低表达与总生存期较短显著相关（p=0.003 和 p=0.004）。多变量分析显示，FBXL5 低表达（风险比，2.001；p=0.034）与总生存期较短显著相关。
FPN 和 FBXL5 可作为晚期 ccRCC 的潜在预后标志物和治疗靶点。
