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

 Cheol Keun Park  ;  Jayoon Heo  ;  Won Sik Ham  ;  Young-Deuk Choi  ;  Sang Joon Shin  ;  Nam Hoon Cho 
 CANCER RESEARCH AND TREATMENT, Vol.53(4) : 1174-1183, 2021-10 
Journal Title
Issue Date
Clear cell renal cell carcinoma ; F-Box and leucine rich repeat protein 5 ; Ferroportin ; Immunohistochemistry ; Prognosis
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Park, Cheol Keun(박철근) ORCID logo https://orcid.org/0000-0001-7689-0386
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Choi, Young Deuk(최영득) ORCID logo https://orcid.org/0000-0002-8545-5797
Ham, Won Sik(함원식) ORCID logo https://orcid.org/0000-0003-2246-8838
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