Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags.
Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags.
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DOI：
10.1038/bjc.2016.295
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发表时间：
2016-10-11
影响因子：
8.8
通讯作者：
Nomura, Fumio
中科院分区：
文献类型：
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作者：
Sogawa, Kazuyuki;Takano, Shigetsugu;Iida, Fumie;Satoh, Mamoru;Tsuchida, Sachio;Kawashima, Yusuke;Yoshitomi, Hideyuki;Sanda, Akihiro;Kodera, Yoshio;Takizawa, Hirotaka;Mikata, Rintaro;Ohtsuka, Masayuki;Shimizu, Hiroaki;Miyazaki, Masaru;Yokosuka, Osamu;Nomura, Fumio
由于缺乏特异性的早期诊断标记物，胰腺导管腺癌(PDAC)仍然是一种毁灭性的疾病。为了改善结果，正在开发蛋白质组学方法来发现PDAC的新生物标记物。使用串联质量标记和LC-MS/MS，我们对PDAC患者手术前和术后的血清进行了对比分析，以确定PDAC的特定血清生物标志物。在验证研究中，我们评估了候选蛋白质的区分能力。在分析的302个蛋白质中，20个被确定为潜在的生物标志物，C4b结合蛋白α链(C4BPA)和聚合物免疫球蛋白受体(PIGR)被选作进一步分析。PDAC患者术前血清C4BPA和PIGR水平显著高于术后(P<0.008，P<0.036)。此外，慢性阻塞性肺疾病患者的血清C4BPA水平显著高于健康对照组、胰腺炎患者和包括胆道癌在内的其他恶性肿瘤患者(P<；0.001)。受试者C_4BPA曲线下面积为0.860，CA_(19-9)为0.846，C_4BPA和CA_(19-9)联合为0.930。C4BPA的AUC值为0.912，CA19-9的AUC为0.737，C4BPA为0.854，CA19-9为0.264。我们已经证明，C4BPA是一种新的血清生物标志物，可用于检测早期PDAC，以及用于区分PDAC与其他胃肠道肿瘤。在大型队列研究中的进一步分析将保证C4BPA作为PDAC临床应用的一个有前途的生物标记物。
Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease due to the lack of specific early diagnostic markers. To improve the outcomes, proteomic approaches are being developed for the discovery of novel biomarkers of PDAC. Using tandem mass tag labelling and LC-MS/MS, we performed comparative analyses of pre- and postoperative sera from PDAC patients to identify specific serum biomarkers for PDAC. In validation studies, we evaluated the discriminatory power of candidate proteins. Among the 302 proteins analysed, 20 were identified as potential biomarkers, with C4b-binding protein α-chain (C4BPA) and polymeric immunoglobulin receptor (PIGR) being selected for further analysis. The sera levels of C4BPA and PIGR were significantly higher in the preoperative PDAC patients than in the postoperative ones (P<0.008, P<0.036, respectively). In addition, serum C4BPA levels, but not PIGR, in patients with PDAC were significantly higher than those in healthy controls as well as in patients with pancreatitis and other malignancies including biliary tract cancers (BTC) (P<0.001). The respective area under the receiver operator characteristics (ROC) curve (AUC) was 0.860 for C4BPA, 0.846 for CA19-9 and 0.930 for the combination of C4BPA and CA19-9 in PDAC vs non-cancer individuals. The respective AUC was 0.912 for C4BPA, 0.737 for CA19-9 in Stages I and II of PDAC, 0.854 for C4BPA and 0.264 for CA19-9 in PDAC vs BTC. We have demonstrated that C4BPA is a novel serum biomarker for detecting early stage PDAC, as well as for distinguishing PDAC from other gastroenterological cancers. Further analysis in large cohort studies will warrant C4BPA as a promising biomarker of PDAC in clinical use.
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影响因子：
4.7
作者：
Mikami M;Tanabe K;Matsuo K;Miyazaki Y;Miyazawa M;Hayashi M;Asai S;Ikeda M;Shida M;Hirasawa T;Kojima N;Sho R;Iijima S
通讯作者：
Iijima S
影响因子：
32.4
作者：
Brodeur, SR;Angelini, F;Geha, RS
通讯作者：
Geha, RS
影响因子：
4.4
作者：
Arntzen, Magnus O.;Koehler, Christian J.;Thiede, Bernd
通讯作者：
Thiede, Bernd
影响因子：
8.8
作者：
Takano, S.;Sogawa, K.;Miyazaki, M.
通讯作者：
Miyazaki, M.
DOI：
10.1007/978-1-4939-0685-7_12
发表时间：
2014-01-01
期刊：
SHOTGUN PROTEOMICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
O'Brien, Darragh P.;Timms, John F.
通讯作者：
Timms, John F.