J-Oil Mills Inc., 11, Kagetoricho, Totsuka-ku, Yokohama, Kanagawa, 245-0064, Japan.
Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan.
Glycoconj J. 2017 Aug;34(4):537-544. doi: 10.1007/s10719-017-9772-9. Epub 2017 Apr 28.
An increase in Lewis- and core-type fucosylation of haptoglobin has been reported in patients with pancreatic cancer (PC), suggesting that fucosylated haptoglobin is a candidate PC biomarker. Previously, we developed a Pholiota squarrosa lectin antibody enzyme-linked immunosorbent assay (PhoSL-ELISA) system for the detection of core-fucosylated haptoglobin. However, with this methodology, positive results were only obtained for some patients with PC, demonstrating the need for a more sensitive detection system. In the current study, we developed an improved PhoSL-ELISA system with higher sensitivity to detect core-fucosylated haptoglobin using high-concentration urea as a denaturing agent with lectin to facilitate detection. We then reevaluated the performance of PhoSL reactive-core-fucosylated haptoglobin (PhoSL-HP) as a PC biomarker using the improved PhoSL-ELISA system. PhoSL-HP levels in the sera of patients with PC were significantly higher than those in healthy volunteers, with an area under the curve (AUC) value of 0.753. Furthermore, the AUC value of CA19-9 improved from 0.793 to 0.907 when combined with PhoSL-HP. Additionally, several CA19-9-negative cases among the patients with PC were diagnosed as positive for PhoSL-HP. In conclusion, PhoSL-HP detection using our improved ELISA system might allow PhoSL-HP to serve as a potential biomarker for PC and thus might be useful to complement the detection of CA19-9 in PC diagnosis.
已有研究报道,胰腺癌(PC)患者的结合珠蛋白 Lewis 型和核心型岩藻糖基化增加,表明岩藻糖化结合珠蛋白是 PC 的候选生物标志物。此前,我们开发了一种鳞伞科漆树凝集素抗体酶联免疫吸附测定(PhoSL-ELISA)系统来检测核心岩藻糖化结合珠蛋白。然而,使用该方法仅能从部分 PC 患者中获得阳性结果,这表明需要一种更敏感的检测系统。在本研究中,我们使用高浓度尿素作为变性剂,并利用凝集素来提高检测的灵敏度,开发了一种改良的 PhoSL-ELISA 系统,以检测核心岩藻糖化结合珠蛋白。然后,我们使用改良的 PhoSL-ELISA 系统重新评估 PhoSL 反应性核心岩藻糖化结合珠蛋白(PhoSL-HP)作为 PC 生物标志物的性能。PC 患者血清中的 PhoSL-HP 水平明显高于健康志愿者,曲线下面积(AUC)值为 0.753。此外,当与 PhoSL-HP 联合使用时,CA19-9 的 AUC 值从 0.793 提高到 0.907。此外,在 PC 患者中,一些 CA19-9 阴性病例被诊断为 PhoSL-HP 阳性。综上所述,使用我们改良的 ELISA 系统检测 PhoSL-HP 可能使 PhoSL-HP 成为 PC 的潜在生物标志物,从而有助于补充 CA19-9 在 PC 诊断中的检测。