A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression.

A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression.
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DOI:
10.1172/jci19617
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发表时间:
2004-04
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
J. Cerutti;R. Delcelo;M. Amadei;Cláudia C. D. Nakabashi;R. Maciel;B. Peterson;J. Shoemaker;G. Riggins
J. Cerutti;R. Delcelo;M. Amadei;Cláudia C. D. Nakabashi;R. Maciel;B. Peterson;J. Shoemaker;G. Riggins
中科院分区:
其他
文献类型:
--
作者:
J. Cerutti;R. Delcelo;M. Amadei;Cláudia C. D. Nakabashi;R. Maciel;B. Peterson;J. Shoemaker;G. Riggins

文献摘要

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甲状腺肿瘤的准确诊断具有挑战性。一个特别的问题是区分滤泡性甲状腺癌(FTC)和良性滤泡性甲状腺腺瘤(FTA),在这两种情况下,细针吸取物的组织学并不确定。通常有必要切除健康的甲状腺,以排除癌症。为了寻找提高诊断的标记物,我们量化了甲状腺癌、甲状腺癌和正常甲状腺的基因转录表达,发现了73个差异表达的转录本(P<OR=0.0001)。使用一组独立的23个FTC、FTA和匹配的正常甲状腺,通过实时RT-PCR检测了17个表达差异较大的基因。四个基因(DDIT3、ARG2、ITM1和C1orf24)在FTC和FTA两类之间存在差异,表达水平的线性组合将FTC与FTA区分开来,估计预测准确率为0.83。此外,免疫组织化学显示,DDIT3和ARG2在59个滤泡性肿瘤中的表达一致(估计一致性,0.76;95%可信区间,[0.59,0.93])。一种基于这些标志物组合的简单测试可能会改善甲状腺结节的术前诊断,从而做出更好的治疗决定,并降低长期医疗成本。
Accurate diagnosis of thyroid tumors is challenging. A particular problem is distinguishing between follicular thyroid carcinoma (FTC) and benign follicular thyroid adenoma (FTA), where histology of fine-needle aspirates is not conclusive. It is often necessary to remove healthy thyroid to rule out carcinoma. In order to find markers to improve diagnosis, we quantified gene transcript expression from FTC, FTA, and normal thyroid, revealing 73 differentially expressed transcripts (P < or = 0.0001). Using an independent set of 23 FTCs, FTAs, and matched normal thyroids, 17 genes with large expression differences were tested by real-time RT-PCR. Four genes (DDIT3, ARG2, ITM1, and C1orf24) differed between the two classes FTC and FTA, and a linear combination of expression levels distinguished FTC from FTA with an estimated predictive accuracy of 0.83. Furthermore, immunohistochemistry for DDIT3 and ARG2 showed consistent staining for carcinoma in an independent set 59 follicular tumors (estimated concordance, 0.76; 95% confidence interval, [0.59, 0.93]). A simple test based on a combination of these markers might improve preoperative diagnosis of thyroid nodules, allowing better treatment decisions and reducing long-term health costs.