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铁调素表达增加在结直肠癌发生过程中的作用

Increased hepcidin expression in colorectal carcinogenesis.

作者信息

Ward Douglas G, Roberts Keith, Brookes Matthew J, Joy Howard, Martin Ashley, Ismail Tariq, Spychal Robert, Iqbal Tariq, Tselepis Chris

机构信息

CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TH, United Kingdom.

出版信息

World J Gastroenterol. 2008 Mar 7;14(9):1339-45. doi: 10.3748/wjg.14.1339.

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 utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation 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.

摘要

目的

研究铁储存调节因子铁调素是否与结肠癌相关贫血有关,以及它在结直肠癌发生过程中是否发挥作用。

方法

采用质谱分析法(基质辅助激光解吸电离飞行时间质谱和表面增强激光解吸电离飞行时间质谱)检测56例结直肠癌患者尿液中的铁调素。运用实时定量逆转录聚合酶链反应测定结直肠癌组织中铁调素mRNA的表达。通过免疫组织化学确定铁调素的细胞定位。

结果

我们发现,虽然尿铁调素表达与贫血无关,但与结直肠癌T分期增加呈正相关(P<0.05)。此外,我们报告铁调素mRNA在34%的结直肠癌组织标本中表达,并与铁转运蛋白抑制相关。结直肠癌组织中的铁调素免疫反应性支持了这一结果。

结论

我们证明全身铁调素表达不太可能是结直肠癌相关全身贫血的原因。然而,我们首次证明结直肠癌组织表达铁调素,这可能代表一种新的致癌信号机制。

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