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岩藻糖化触珠蛋白是一种新型癌症生物标志物,与结直肠癌手术后的预后相关。

Fucosylated haptoglobin is a novel type of cancer biomarker linked to the prognosis after an operation in colorectal cancer.

机构信息

Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Japan.

出版信息

Cancer. 2012 Jun 15;118(12):3036-43. doi: 10.1002/cncr.26490. Epub 2011 Oct 17.

DOI:10.1002/cncr.26490
PMID:22006099
Abstract

BACKGROUND

Fucosylation is a crucial oligosaccharide modification in cancer and inflammation. Total cellular proteins of cancer cells and the sera of patients with cancer both show increased fucosylation levels. Certain kinds of fucosylated proteins can be applied as novel cancer biomarkers in glyco-proteomic analyses. We previously identified fucosylated haptoglobin (Fuc-Hpt) as a serologic marker for pancreatic cancer, and recently developed a lectin-antibody enzyme-linked immunosorbent assay system for quantifying Fuc-Hpt. In the present study, we investigated the clinical outcome of Fuc-Hpt levels in patients with colorectal cancer (CRC), and examined the mechanisms underlying Fut-Hpt production using a murine tumor transplantation model.

METHODS

The relationship between Fuc-Hpt levels and clinical parameters was investigated in 77 patients with CRC, all of whom underwent primary resection. Serum Fuc-Hpt levels were examined in athymic nude mice injected with colon cancer cell lines that lacked fucosylation.

RESULTS

Fuc-Hpt levels were significantly associated with overall and relapse-free survival, distant metastasis, clinical stage, and curability. Multivariate analysis revealed that distant metastasis was an independent factor for increased Fuc-Hpt levels. The combination of Fuc-Hpt and CEA might be a better serologic marker to predict prognosis. Fuc-Hpt levels were higher in mice with direct injection of tumor cells into the spleen than in those injected subcutaneously.

CONCLUSIONS

Fuc-Hpt might be a useful marker for the prognosis of CRC. Fuc-Hpt could be produced by the tissue surrounding tumor cells, which might be the mechanism underlying Fuc-Hpt elevation associated with distant metastasis.

摘要

背景

糖基化是癌症和炎症中一种重要的寡糖修饰。癌细胞的总细胞蛋白和癌症患者的血清都显示出更高的岩藻糖基化水平。某些种类的岩藻糖化蛋白可以作为糖蛋白质组分析中的新型癌症生物标志物。我们之前发现岩藻糖化触珠蛋白(Fuc-Hpt)是胰腺癌的血清标志物,并最近开发了用于定量 Fuc-Hpt 的凝集素-抗体酶联免疫吸附测定系统。在本研究中,我们研究了结直肠癌(CRC)患者 Fuc-Hpt 水平的临床结局,并使用小鼠肿瘤移植模型研究了 Fut-Hpt 产生的机制。

方法

对 77 例接受原发性切除术的 CRC 患者进行了 Fuc-Hpt 水平与临床参数之间的关系研究。在注射缺乏岩藻糖基化的结肠癌细胞系的裸鼠中检测血清 Fuc-Hpt 水平。

结果

Fuc-Hpt 水平与总生存期和无复发生存期、远处转移、临床分期和可治愈性显著相关。多变量分析显示,远处转移是 Fuc-Hpt 水平升高的独立因素。Fuc-Hpt 和 CEA 的组合可能是预测预后的更好的血清标志物。将肿瘤细胞直接注射到脾脏中的小鼠的 Fuc-Hpt 水平明显高于皮下注射的小鼠。

结论

Fuc-Hpt 可能是 CRC 预后的有用标志物。Fuc-Hpt 可能是由肿瘤细胞周围的组织产生的,这可能是与远处转移相关的 Fuc-Hpt 升高的机制。

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