Colorectal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 7, 2008; 14(9): 1339-1345
Published online Mar 7, 2008. doi: 10.3748/wjg.14.1339
Increased hepcidin expression in colorectal carcinogenesis
Douglas G Ward, Keith Roberts, Matthew J Brookes, Howard Joy, Ashley Martin, Tariq Ismail, Robert Spychal, Tariq Iqbal, Chris Tselepis
Douglas G Ward, Keith Roberts, Matthew J Brookes, Howard Joy, Ashley Martin, Tariq Ismail, Robert Spychal, Tariq Iqbal, Chris Tselepis, CRUK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TH, United Kingdom
Author contributions: Ward DG performed all the mass spectrometry experiments and along with Martin A was involved in data analysis; Roberts K and Brookes MJ performed the Real Time RT-PCR and immunohistochemistry experiments; Joy H and Ismail T were crucial in sample collection; Spychal R provided funding for this research; Iqbal T and Tselepis C designed the experiments, did the data analysis and wrote the manuscript.
Correspondence to: Dr. Chris Tselepis, CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TH, United Kingdom. c.tselepis@bham.ac.uk
Telephone: +44-121-4142972
Fax: +44-121-6272384
Received: December 3, 2007
Revised: January 22, 2008
Published online: March 7, 2008
Abstract

AIM: To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis.

METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilized to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localization was determined using immunohistochemistry.

RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was positively associated with increasing T-stage of colorectal cancer (P < 0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repression. This was supported by hepcidin immunoreactivity in colorectal cancer tissue.

CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.

Keywords: Iron; Hepcidin; Colon; Cancer; Anaemia; Mass spectrometry