Aberrant glycosylation associated with enzymes as cancer biomarkers.
Aberrant glycosylation associated with enzymes as cancer biomarkers.
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DOI：
10.1186/1559-0275-8-7
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发表时间：
2011-06-03
影响因子：
3.8
通讯作者：
Chan DW
中科院分区：
文献类型：
--
作者：
Meany DL;Chan DW
酶在个性化医疗中的新角色之一是建立在使用酶相关异常糖基化发现癌症生物标志物的合理方法上。作为癌症的标志，异常糖基化与诸如糖基转移酶和糖苷酶的酶的差异表达相关。这些酶的异常表达反过来又导致癌细胞产生具有聚糖结构中的特定癌症相关畸变的糖蛋白。在这篇综述中，我们提供了在三个领域使用异常糖基化发现癌症生物标志物的例子。首先，糖基化机制如糖基转移酶/糖苷酶的变化可用作癌症生物标志物。其次，大多数临床上有用的癌症生物标志物是糖蛋白。在这些现有生物标志物的聚糖结构中发现特定的癌症相关畸变可以提高其癌症特异性，例如发现AFP-L3，AFP的岩藻糖基化糖型。第三，癌症相关的聚糖结构畸变为使用糖组学和糖蛋白组学技术发现新的生物标志物提供了令人信服的理由。作为癌症的标志，异常糖基化允许生物标志物发现工作的合理设计。但更重要的是，我们需要使用良好的策略将这些生物标志物从发现转化为临床诊断，例如将使用蛋白质组学技术发现的生物标志物转化为OVA 1的经验教训，这是FDA批准的第一个体外诊断多变量指数测定（IVDMIA）。这些经验教训，提供了重要的指导，在生物标志物的发现和翻译，目前的努力，适用于发现异常糖基化与酶作为癌症生物标志物以及。
One of the new roles for enzymes in personalized medicine builds on a rational approach to cancer biomarker discovery using enzyme-associated aberrant glycosylation. A hallmark of cancer, aberrant glycosylation is associated with differential expressions of enzymes such as glycosyltransferase and glycosidases. The aberrant expressions of the enzymes in turn cause cancer cells to produce glycoproteins with specific cancer-associated aberrations in glycan structures. In this review we provide examples of cancer biomarker discovery using aberrant glycosylation in three areas. First, changes in glycosylation machinery such as glycosyltransferases/glycosidases could be used as cancer biomarkers. Second, most of the clinically useful cancer biomarkers are glycoproteins. Discovery of specific cancer-associated aberrations in glycan structures of these existing biomarkers could improve their cancer specificity, such as the discovery of AFP-L3, fucosylated glycoforms of AFP. Third, cancer-associated aberrations in glycan structures provide a compelling rationale for discovering new biomarkers using glycomic and glycoproteomic technologies. As a hallmark of cancer, aberrant glycosylation allows for the rational design of biomarker discovery efforts. But more important, we need to translate these biomarkers from discovery to clinical diagnostics using good strategies, such as the lessons learned from translating the biomarkers discovered using proteomic technologies to OVA 1, the first FDA-cleared In Vitro Diagnostic Multivariate Index Assay (IVDMIA). These lessons, providing important guidance in current efforts in biomarker discovery and translation, are applicable to the discovery of aberrant glycosylation associated with enzymes as cancer biomarkers as well.