TFF3-based candidate gene discrimination of benign and malignant thyroid tumors in a region with borderline iodine deficiency
TFF3-based candidate gene discrimination of benign and malignant thyroid tumors in a region with borderline iodine deficiency
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DOI：
10.1210/jc.2006-1255
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发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Fuhrer, Dagmar
中科院分区：
文献类型：
--
作者：
Krause, Kerstin;Eszlinger, Markus;Fuhrer, Dagmar
背景资料：随着微阵列技术的出现，越来越多的标记基因被提出来区分甲状腺良恶性病变。然而，大多数标记物有待通过独立研究确认。在这篇论文中，我们重新评估了10个候选基因在边缘缺碘地区甲状腺良性和恶性病变中的诊断潜力。方法：对150例甲状腺标本中的CCND 2、PLAB、PCSK 2、HGD 1、TFF 3、B4 GALT、LGALS 3、ETS 1、ADM 3和TG进行实时定量PCR，包括52个良性甲状腺结节结果：甲状腺癌患者甲状腺组织中滤泡状腺瘤28例，腺瘤性结节24例，正常甲状腺组织52例，滤泡状癌20例，乳头状癌20例，未分化癌6例。在单个基因的基础上，TFF 3，PLAB和ADM 3在良性甲状腺结节和甲状腺恶性肿瘤中的mRNA表达存在显着差异。使用两个标记基因集，我们确定了11个组合，这使得良性和恶性甲状腺结节的区别和滤泡性腺瘤和癌的歧视。然而，对于癌症预测，每个样本至少分析六个基因是必要的，并且允许在最具区分性的集合中以94%的准确率正确预测良性甲状腺病变和甲状腺癌。（TFF3/PLAB/TG/ADM3/HGD1/LGALS 3）。我们证实了一些最近提出的标记基因用于区分甲状腺良恶性肿瘤的适用性，并建议它们的诊断有用性与碘的供应无关。我们建议，在我们的验证研究中确定的最具鉴别力的标志物集以及其他研究者提出的标志物组合，现在应该在多中心试验中进行评估。
Background: With the advent of microarray technology, increasing numbers of marker genes are proposed to distinguish benign and malignant thyroid lesions. However, most markers await confirmation through independent studies. In this paper, we re-evaluate the diagnostic potential of 10 proposed candidate genes in benign and malignant thyroid pathologies in a region with borderline iodine deficiency.Methods: Quantitative real-time PCR was performed for CCND2, PLAB, PCSK2, HGD1, TFF3, B4GALT, LGALS3, ETS1, ADM3, and TG in 150 thyroid specimens, including 52 benign thyroid nodules (28 follicular adenoma and 24 adenomatous nodules), 52 corresponding normal thyroid tissues, 20 follicular carcinomas, 20 papillary carcinomas, and six undifferentiated carcinomas.Results: On a single-gene basis, significant differences in mRNA expression were found for TFF3, PLAB, and ADM3 in benign thyroid nodules and thyroid malignancy. Using two-marker gene sets, we identified 11 combinations, which allowed both a distinction of benign and malignant thyroid nodules and a discrimination of follicular adenoma and carcinoma. However, for cancer prediction, analysis of a minimum of six genes per sample was necessary and allowed correct prediction of a benign thyroid lesion and thyroid cancer with 94% accuracy in the most discriminative set (TFF3/PLAB/TG/ADM3/HGD1/LGALS3).Conclusion: We confirm the applicability of a number of recently proposed marker genes for the distinction of benign and malignant thyroid tumor and suggest that their diagnostic usefulness is independent of the iodide supply. We propose that the most discriminative marker set identified in our validation study together with marker combinations proposed by other investigators should now be evaluated in multicenter trials.