Haptoglobin phenotype is a critical factor in the use of fucosylated haptoglobin for pancreatic cancer diagnosis
Haptoglobin phenotype is a critical factor in the use of fucosylated haptoglobin for pancreatic cancer diagnosis
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DOI：
10.1016/j.cca.2018.09.001
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发表时间：
2018-12-01
影响因子：
5
通讯作者：
Miyoshi, Eiji
中科院分区：
文献类型：
--
作者：
Morishita, Koichi;Ito, Nami;Miyoshi, Eiji
聚焦化是与癌症和炎症有关的最重要的糖基化之一。许多研究报道了多种癌症患者血清聚焦型触珠蛋白（Fuc-Hpt）的显著升高。在这项研究中，我们使用一种凝集素抗体酶联免疫吸附试验（ELISA）或一种新的ELISA系统来测量Fuc-Hpt，该系统使用了Fuc-Hpt的聚糖抗体。已知Hpt根据其遗传背景分为三种表型（Hpt1-1， Hpt2-1和Hpt2-2）。血清Hpt的正常水平在每种Hpt表型中是不同的，这些表型与几种人类疾病的发病率有关。在这里，我们研究了Hpt表型如何影响Fuc-Hpt的测量，使用两种ELISA。有趣的是，我们发现在两种类型的ELISA中，Hpt1-1表型的血清Fuc-Hpt水平显著降低。对于Hpt2-1和Hpt2-2，我们观察到胰腺癌患者血清Fuc-Hpt水平显著升高。当Hpt1-1表型的病例减少时，我们的受试者工作特征（ROC）曲线分析显示，每次ELISA诊断胰腺癌的曲线下面积（AUC）值都增加。综上所述，我们的研究结果表明，Hpt表型对于Fuc-Hpt作为癌症生物标志物的临床应用至关重要。
Fucosylation is one of the most important glycosylations involved in cancer and inflammation. Many studies have reported significant increases in serum fucosylated haptoglobin (Fuc-Hpt) in a variety of cancer patients. In this study, we measured Fuc-Hpt using a lectin-antibody enzyme-linked immunosorbent assay (ELISA) or a novel ELISA system that used a glycan antibody for Fuc-Hpt. Hpt is known to be divided into three phenotypes (Hpt1-1, Hpt2-1, and Hpt2-2), depending on its genetic background. Normal levels of serum Hpt are different in each Hpt phenotype and these phenotypes are associated with the incidence of several human diseases. Here, we investigated how Hpt phenotype affected measurements of Fuc-Hpt, using two kinds of ELISA. Interestingly, we found that serum Fuc-Hpt levels were dramatically lower in the Hpt1-1 phenotype for both types of ELISA. For Hpt2-1 and Hpt2-2, we observed significantly increased serum Fuc-Hpt levels in patients with pancreatic cancer. When cases of the Hpt1-1 phenotype were depleted, our receiver operating characteristic (ROC) curve analyses showed that the area under the curve (AUC) value for pancreatic cancer diagnosis increased in each ELISA. Taken together, our results indicate that Hpt phenotype is a critical for the clinical application of Fuc-Hpt as a cancer biomarker.