Detection of the potential pancreatic cancer marker MUC4 in serum using surface-enhanced Raman scattering.
Detection of the potential pancreatic cancer marker MUC4 in serum using surface-enhanced Raman scattering.
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DOI：
10.1021/ac102829b
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发表时间：
2011-04-01
影响因子：
7.4
通讯作者：
Porter, Marc D.
中科院分区：
文献类型：
--
作者：
Wang, Gufeng;Lipert, Robert J.;Jain, Maneesh;Kaur, Sukhwinder;Chakraboty, Subhankar;Torres, Maria P.;Batra, Surinder K.;Brand, Randall E.;Porter, Marc D.
胰腺癌(PC)是最致命的恶性肿瘤之一。它的5年存活率只有6%，部分原因是缺乏可靠的早期诊断肿瘤标志物。最近的研究表明，粘蛋白MUC4在胰腺癌细胞系和组织中异常表达，但在正常胰腺和慢性胰腺炎中检测不到。因此，患者血清中MUC4水平有可能作为PC的诊断和预后标志物。然而，使用常规检测平台(例如，酶联免疫吸附试验(ELISA)和放射免疫分析(RIA))测定血清中MUC4的方法并不成功。这阻碍了对该蛋白作为血清中可能的PC标志物的实用性的评估。为了解决这一障碍，本文的工作检验了通过开发基于表面增强拉曼散射(SERS)的免疫分析来创建对MUC4的简单诊断测试的可能性，该免疫分析随后被用于证明首次在癌症患者血清样本中检测到MUC4。重要的是，这些测量表明，与健康人和良性疾病患者的血清相比，PC患者的血清对MUC4产生了显著更高的SERS反应。这些结果表明，基于SERS的免疫测定可以监测患者血清中MUC4的水平，这是评估该蛋白作为PC早期诊断的血清标志物的潜力所必需的第一步。本文详细介绍了这些和其他发现(即粘蛋白CA19-9的检测)，这些结果表明我们的SERS方法在检测极限、读出时间和所需样本量方面优于传统的分析方法(即RIA和ELISA)。
Pancreatic cancer (PC) is one of the most lethal malignancies. It has a 5-year survival rate of only 6%, owing in part to the lack of a reliable tumor marker for early diagnosis. Recent research has shown that the mucin protein MUC4 is aberrantly expressed in pancreatic adenocarcinoma cell lines and tissues but is undetectable in normal pancreas and chronic pancreatitis. Thus, the level of MUC4 in patient sera has the potential to function as a diagnostic and prognostic marker for PC. However, the measurement of MUC4 in sera using conventional test platforms (e.g., enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA)) has been unsuccessful. This has prevented the assessment of the utility of this protein as a possible PC marker in sera. In addressing this obstacle, the work herein examines the potential to create a simple diagnostic test for MUC4 through the development of a surface-enhanced Raman scattering (SERS)-based immunoassay, which was then used to demonstrate the first ever detection of MUC4 in cancer patient serum samples. Importantly, these measurements showed that sera from patients with PC produced a significantly higher SERS response for MUC4 compared to sera from healthy individuals and from patients with benign diseases. These results indicate that a SERS-based immunoassay can monitor MUC4 levels in patient sera, representing a much needed first step toward assessing the potential of this protein to serve as a serum marker for the early stage diagnosis of PC. This paper details these and other findings (i.e., the detection of the mucin protein CA19-9), which demonstrate that our SERS assay outperforms conventional assays (i.e., RIA and ELISA) with respect to limits of detection, readout time, and required sample volume.
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