Shirai Yoshihiko, Sogawa Kazuyuki, Yamaguchi Taketo, Sudo Kentaro, Nakagawa Akihiko, Sakai Yuji, Ishihara Takeshi, Sunaga Masahiko, Nezu Masahiko, Tomonaga Takeshi, Miyazaki Masaru, Saisho Hiromitsu, Nomura Fumio
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Hepatogastroenterology. 2008 Sep-Oct;55(86-87):1824-9.
BACKGROUND/AIMS: Malignant intraductal papillary mucinous neoplasm of the pancreas (IPMN) has a very poor prognosis, and there is no useful biomarker for an early diagnosis at present. A biomarker is expected to allow an early diagnosis of IPMNs and consequently lead to an improvement of the patients' prognosis. Recent advances in proteomic analysis are remarkable; therefore we explored novel biomarkers for IPMN using Surface-Enhanced Laser Desorption and Ionization (SELDI) Mass Spectrometry.
We collected pancreatic juice samples from 33 patients with IPMNs, 54 patients with pancreatic ductal carcinoma, and 31 with chronic pancreatitis. We analyzed the pancreatic juice samples using a SELDI ProteinChip system (Ciphergen Biosystems, Fremont, CA).
We identified a 6240-Da peak whose expression in pancreatic juice from patients with IPMNs was significantly higher compared with that in other pancreatic diseases (P<0.01). This 6240-Da protein was partially purified and was identified as pancreatic secretory trypsin inhibitor (PSTI) by amino acid sequencing. The pancreatic juice PSTI levels, as measured by radioimmunoassay, were significantly higher in the IPMN group than in the other groups (P<0.001). When the diagnostic cutoff value of PSTI in pancreatic juice was set at 25000 ng/mL, the positive predictive value, negative predictive value, sensitivity, and specificity were respectively 89%, 83%, 48%, and 98%.
PSTI levels of pancreatic juice in patients with IPMN were significantly higher than those in patients with other pancreatic diseases. The PSTI level in pancreatic juice may be useful for the diagnosis of IPMN.
背景/目的：胰腺导管内乳头状黏液性肿瘤（IPMN）恶性程度高，预后很差，目前尚无有效的早期诊断生物标志物。有望找到一种生物标志物实现IPMN的早期诊断，从而改善患者预后。蛋白质组学分析近来进展显著，因此我们采用表面增强激光解吸电离（SELDI）质谱技术探寻IPMN的新型生物标志物。
我们收集了33例IPMN患者、54例胰腺导管癌患者及31例慢性胰腺炎患者的胰液样本。使用SELDI蛋白质芯片系统（Ciphergen生物系统公司，弗里蒙特，加利福尼亚州）分析这些胰液样本。
我们鉴定出一个分子量为6240道尔顿的峰，IPMN患者胰液中该峰的表达明显高于其他胰腺疾病患者（P<0.01）。对该分子量为6240道尔顿的蛋白质进行了部分纯化，并通过氨基酸测序鉴定为胰腺分泌型胰蛋白酶抑制剂（PSTI）。放射免疫法检测显示，IPMN组胰液中的PSTI水平显著高于其他组（P<0.001）。当将胰液中PSTI的诊断临界值设定为25000 ng/mL时，其阳性预测值、阴性预测值、敏感性和特异性分别为89%、83%、48%和98%。
IPMN患者胰液中的PSTI水平显著高于其他胰腺疾病患者。胰液中的PSTI水平可能有助于IPMN的诊断。
