Protein profiling in pancreatic juice for detection of intraductal papillary mucinous neoplasm of the pancreas.

Protein profiling in pancreatic juice for detection of intraductal papillary mucinous neoplasm of the pancreas.
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胰液中的蛋白质分析用于检测胰腺导管内乳头状粘液性肿瘤。

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发表时间:
2008
影响因子:
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通讯作者:
F. Nomura
F. Nomura
中科院分区:
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作者:
Y. Shirai;K. Sogawa;Taketo Yamaguchi;K. Sudo;A. Nakagawa;Yuji Sakai;T. Ishihara;M. Sunaga;M. Nezu;T. Tomonaga;M. Miyazaki;H. Saisho;F. Nomura

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背景/目的 胰腺导管内乳头状黏液性恶性肿瘤(IPMN)预后极差,目前尚无有效的生物标志物用于早期诊断。生物标志物预计将能够早期诊断IPMNs,从而改善患者的预后。蛋白质组学分析的最新进展是显着的,因此,我们探索新的生物标志物IPMN使用表面增强激光解吸电离(SELDI)质谱。 方法 我们收集了33例IPMN患者、54例胰腺导管癌患者和31例慢性胰腺炎患者的胰液样本。我们使用SELDI蛋白质芯片系统(Ciphergen Biosystems,Fremont,CA)分析胰液样品。 结果 我们发现一个6240-Da的峰,其在IPMNs患者的胰液中的表达显著高于其他胰腺疾病(P<0.01)。该蛋白分子量为6240-Da,经部分纯化后,经氨基酸序列测定,鉴定为胰腺分泌型胰蛋白酶抑制剂(PSTI)。用放射免疫法测定的胰液PSTI水平,IPMN组明显高于其他各组(P<0.001)。以25000 ng/mL作为诊断临界值,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%。 结论 IPMN患者的胰液PSTI水平显著高于其他胰腺疾病患者。胰液中PSTI水平对诊断IPMN有一定的参考价值。
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. METHODOLOGY 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). RESULTS 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%. CONCLUSIONS 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.