Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

Takao Kamai,Kyoko Arai,Hideyuki Abe,Naohisa Tomosugi,Ken-Ichiro Yoshida

doi:10.1186/1471-2407-9-270

Takao Kamai, Kyoko Arai + Show 3 more

Open Access

https://doi.org/10.1186/1471-2407-9-270

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Abstract

BackgroundHepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC).MethodsWe measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction.ResultsThe serum hepcidin-25 level was higher in patients with metastatic RCC than nonmetastatic RCC (P < 0.0001), and was positively correlated with the serum interleukin-6 and C-reactive protein levels (P < 0.001). Expression of hepcidin mRNA was lower in tumor tissues than in non-tumor tissues (P < 0.0001). The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue specimens from 32 patients. Hepcidin mRNA expression in tumor tissue was correlated with metastatic potential, but not with histological differentiation or tumor stage. Kaplan-Meier analysis showed that over expression of hepcidin mRNA was related to shorter overall survival in RCC patients. Univariate analysis (Cox proportional hazards model) showed that the hepcidin mRNA level was an independent prognostic factor for overall survival.ConclusionOur findings suggest that a high serum hepcidin-25 level may indicate the progression of RCC, and that upregulation of hepcidin mRNA expression in tumor tissue may be related to increased metastatic potential.

Highlights

Hepcidin has an important role in iron metabolism
The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue samples from 32 patients
Ganz et al reported that serum hepcidin levels were increased in patients who had inflammation and an elevated serum C-reactive protein (CRP) level, multiple myeloma, or chronic kidney disease, indicating that hepcidin is influenced by physiologic, pathologic, and genetic factors, and that it provides useful information about the etiology of iron disorders [29]. It remains unclear how elevation of serum hepcidin-25 reflects and/ or is involved in the progression of renal cell carcinoma (RCC), but our observations showed that the serum hepcdin-25 level was correlated with the levels of IL-6 and CRP and that elevation of all three factors was associated with metastasis of RCC

Summary

Introduction

We investigated whether hepcidin was involved in renal cell carcinoma (RCC). Renal cell carcinoma (RCC) is the most common malignant tumor of the kidneys and the third most common malignancy in the urological field. More than 50% of all RCCs are found incidentally, which results in a high percentage of patients with metastasis at the time of diagnosis [1]. Better understanding of the biology and genetics of RCC have shed light on possible targeted approaches to metastatic disease [5]. The pathway involving the Hipple-Lindau (VHL) tumor suppressor gene, hypoxia-inducible factor-1 (HIF-1) alpha, and vascular endothelial growth factor (VEGF) is important for the growth of clear cell RCC, and targeting this pathway is a novel approach to the treatment of metastatic RCC

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