Glycoprotein microarrays with multi-lectin detection: Unique lectin binding patterns as a tool for classifying normal, chronic pancreatitis and pancreatic cancer sera
Glycoprotein microarrays with multi-lectin detection: Unique lectin binding patterns as a tool for classifying normal, chronic pancreatitis and pancreatic cancer sera
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DOI：
10.1021/pr070062p
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Lubman, David M.
中科院分区：
文献类型：
--
作者：
Zhao, Jia;Patwa, Tasneem H.;Lubman, David M.
胰腺癌是美国癌症相关死亡的第四大原因，5年生存率低于4%。有效的早期检测和筛查目前不可用，并且肿瘤通常在晚期诊断，通常在转移后。胰腺癌的现有临床标志物缺乏特异性，因为它们也存在于胰腺和胆道的炎性疾病中。在这里所描述的工作中，天然存在的糖蛋白通过使用凝集素亲和层析富集，然后通过无孔反相层析进一步解析。然后打印糖蛋白微阵列，并用各种凝集素进行探测，以筛选正常、慢性胰腺炎和胰腺癌患者血清中的糖基化模式。对10例正常人、8例慢性胰腺炎患者和6例胰腺癌患者的血清进行了研究。使用生物信息学方法，包括主成分分析（PCA）和层次聚类（HC）的糖蛋白微阵列的数据进行了分析。正常和慢性胰腺炎血清被发现聚集在一起，虽然在两个不同的组，而胰腺癌血清显着不同的其他两组。唾液酸化和岩藻糖基化作为癌症的函数在几种蛋白质上增加，包括血液结合蛋白、激肽原-1、抗凝血酶-III和结合珠蛋白相关蛋白，而在血浆蛋白酶C1抑制剂上检测到唾液酸化减少。通过凝集素印迹实验和使用μ LC-ESI-TOF的肽图谱实验验证糖基化的靶改变。这些改变的聚糖结构可能有助于胰腺癌和慢性胰腺炎的鉴别诊断，并识别来自不同临床状况患者的生物样本之间的关键差异。关键词：作者请提供关键词
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with a 5-year survival rate of less than 4%. Effective early detection and screening are currently not available, and tumors are typically diagnosed at a late stage, frequently after metastasis. Existing clinical markers of pancreatic cancer lack specificity, as they are also found in inflammatory diseases of the pancreas and biliary tract. In the work described here, naturally occurring glycoproteins were enriched by using lectin affinity chromatography and then further resolved by nonporous reversed-phase chromatography. Glycoprotein microarrays were then printed and probed with a variety of lectins to screen glycosylation patterns in sera from normal, chronic pancreatitis, and pancreatic cancer patients. Ten normal, 8 chronic pancreatitis, and 6 pancreatic cancer sera were investigated. Data from the glycoprotein microarrays were analyzed using bioinformatics approaches including principal component analysis (PCA) and hierarchical clustering (HC). Both normal and chronic pancreatitis sera were found to cluster close together, although in two distinct groups, whereas pancreatic cancer sera were significantly different from the other two groups. Both sialylation and fucosylation increased as a function of cancer on several proteins including Hemopexin, Kininogen-1, Antithrombin-III, and Haptoglobin-related protein, whereas decreased sialylation was detected on plasma protease C1 inhibitor. Target alterations on glycosylations were verified by lectin blotting experiments and peptide mapping experiments using mu LC-ESI-TOF. These altered glycan structures may have utility for the differential diagnosis of pancreatic cancer and chronic pancreatitis and identify critical differences between biological samples from patients with different clinical conditions.Keywords: AUTHOR PLEASE PROVIDE KEYWORDS