Ueda Makiko, Kamada Yoshihiro, Takamatsu Shinji, Shimomura Mayuka, Maekawa Tomohiro, Sobajima Tomoaki, Fujii Hironobu, Nakayama Kotarosumitomo, Nishino Kimihiro, Yamada Makoto, Kobayashi Yuka, Kumada Takashi, Ito Toshifumi, Eguchi Hidetoshi, Nagano Hiroaki, Miyoshi Eiji
Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
aMs New Otani Clinic, Osaka, Osaka, Japan.
Pancreatology. 2016 Mar-Apr;16(2):238-43. doi: 10.1016/j.pan.2016.01.004. Epub 2016 Jan 21.
BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignancies, and its diagnosis in early stages is the most important prognostic factor. Chronic pancreatitis (CP), a common background of PDAC occurrence, is morphologically defined as progressive pancreatic fibrosis and inflammation accompanied by pancreatic exocrine cell atrophy. We recently found that inflammation and fibrosis are independent characteristic histological changes in noncancerous lesions in PDAC patients despite the absence of a past history of clinical CP. Subclinical CP is an important background for PDAC occurrence. Therefore, there is an urgent need to develop a noninvasive and reliable biomarker for CP diagnosis.
Fifty-nine healthy volunteers (HV), 159 patients with CP, and 83 patients with PDAC were enrolled in this study. We measured serum total fucosylated haptoglobin (Fuc-Hpt) and core-Fuc-Hpt levels using lectin-antibody enzyme-linked immunosorbent assay kits that we developed. In these kits, total Fuc-Hpt and core-Fuc-Hpt were measured using Aleuria aurantia lectin and Pholiota squarrosa lectin, respectively.
Serum Fuc-Hpt levels were significantly increased in CP patients compared to HV (P < 0.0001) and were further increased in PDAC patients (P < 0.0001). Interestingly, serum core-Fuc-Hpt levels were significantly higher in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Multivariate analyses demonstrated that total serum core-Fuc-Hpt was an independent determinant for CP diagnosis, but Fuc-Hpt was not.
A dramatic change in oligosaccharides was observed in serum haptoglobin between CP and PDAC. Serum core-Fuc-Hpt may be a novel and useful biomarker for CP diagnosis.
背景/目的:胰腺导管腺癌(PDAC)是所有恶性肿瘤中预后最差的,其早期诊断是最重要的预后因素。慢性胰腺炎(CP)是PDAC发生的常见背景,在形态学上被定义为进行性胰腺纤维化和炎症,并伴有胰腺外分泌细胞萎缩。我们最近发现,尽管没有临床CP病史,但炎症和纤维化是PDAC患者非癌性病变中独立的特征性组织学变化。亚临床CP是PDAC发生的重要背景。因此,迫切需要开发一种用于CP诊断的非侵入性且可靠的生物标志物。
本研究纳入了59名健康志愿者(HV)、159名CP患者和83名PDAC患者。我们使用自行开发的凝集素-抗体酶联免疫吸附测定试剂盒测量血清总岩藻糖化触珠蛋白(Fuc-Hpt)和核心Fuc-Hpt水平。在这些试剂盒中,分别使用橙黄网孢盘菌凝集素和黄裙竹荪凝集素测量总Fuc-Hpt和核心Fuc-Hpt。
与HV相比,CP患者的血清Fuc-Hpt水平显著升高(P < 0.0001),而PDAC患者的血清Fuc-Hpt水平进一步升高(P < 0.0001)。有趣的是,与HV相比,CP患者的血清核心Fuc-Hpt水平显著更高(P < 0.0001),且高于PDAC患者(P < 0.0001)。多变量分析表明,血清总核心Fuc-Hpt是CP诊断的独立决定因素,但Fuc-Hpt不是。
在CP和PDAC之间观察到血清触珠蛋白中的寡糖有显著变化。血清核心Fuc-Hpt可能是一种用于CP诊断的新型且有用的生物标志物。