Common cancer biomarkers

Common cancer biomarkers
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DOI:
10.1158/0008-5472.can-05-3433
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发表时间:
2006-03-15
期刊:
影响因子:
11.2
通讯作者:
Wang, E
Wang, E
中科院分区:
医学1区
文献类型:
--
作者:
Basil, CF;Zhao, YD;Wang, E

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人们越来越有兴趣用分子工具来补充传统的组织病理学评估,以提高诊断和预后目的的癌症分期的敏感性和特异性。这项研究致力于识别癌症特异性标志物,用于广泛的癌症类型的分子检测。我们使用了373个档案样本,包括不同血统的正常组织和良恶性肿瘤(主要是结肠癌、黑色素瘤、卵巢癌和食道癌)。所有样品以相同的方法处理,并与相同的参考RNA源共杂交到定制的cDNA阵列平台。数据库分为训练集(n=201)和可比预测集(n=172)。留一法交叉验证和基因配对分析确定了恶性病变过度表达的假定癌症生物标记物,独立于衍生组织。特别是,7对基因在区分良恶性病变方面具有很高的预测能力(87%)。基于相同基因的受试者操作员特征曲线能够区分良恶性组织,准确率为94%。这项研究的相关性依赖于有限数量的生物标记物的鉴定,这些标记物普遍存在于不同组织学的癌症中。这是以前从未做过的。这些生物标志物可以广泛用于提高癌症分期的敏感性和准确性,以及早期发现局部或系统性复发。与配对的正常组织相比,它们在癌组织中的选择性表达表明,当目前使用的分化标记物不可靠时,它们与致癌过程有关,导致在疾病进展期间稳定表达。
There is an increasing interest in complementing conventional histopathologic evaluation with molecular tools that could increase the sensitivity and specificity of cancer staging for diagnostic and prognostic purposes. This study strove to identify cancer-specific markers for the molecular detection of a broad range of cancer types. We used 373 archival samples inclusive of normal tissues of various lineages and benign or malignant tumors (predominantly colon, melanoma, ovarian, and esophageal cancers). All samples were processed identically and cohybridized with an identical reference RNA source to a custom-made cDNA array platform. The database was split into training (n = 201) and comparable prediction (n = 172) sets. Leave-one-out cross-validation and gene pairing analysis identified putative cancer biomarkers overexpressed by malignant lesions independent of tissue of derivation. In particular, seven gene pairs were identified with high predictive power (87%) in segregating malignant from benign lesions. Receiver operator characteristic curves based on the same genes could segregate malignant from benign tissues with 94% accuracy. The relevance of this study rests on the identification of a restricted number of biomarkers ubiquitously expressed by cancers of distinct histology. This has not been done before. These biomarkers could be used broadly to increase the sensitivity and accuracy of cancer staging and early detection of locoregional or systemic recurrence. Their selective expression by cancerous compared with paired normal tissues suggests an association with the oncogenic process resulting in stable expression during disease progression when the presently used differentiation markers are unreliable.