Identification of genes differentially expressed in benign versus malignant thyroid tumors
Identification of genes differentially expressed in benign versus malignant thyroid tumors
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DOI：
10.1158/1078-0432.ccr-07-4495
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发表时间：
2008-06-01
影响因子：
11.5
通讯作者：
Zeiger, Martha A.
中科院分区：
文献类型：
--
作者：
Prasad, Nijaguna B.;Somervell, Helina;Zeiger, Martha A.
目的：虽然细针抽吸活检是评估甲状腺结节最有用的诊断工具，但甲状腺结节的术前诊断常常不精确，高达 30% 的细针抽吸活检细胞学样本报告为“可疑”或“不确定”。因此，在术前区分这些病变时需要其他辅助手段，例如基于分子的诊断方法。实验设计：为了确定术前区分这些病变的诊断标记，我们选择通过微阵列分析来研究八种不同的甲状腺肿瘤亚型，这对临床医生提出了诊断挑战。结果：我们对 94 个甲状腺肿瘤进行了基于微阵列的分析，鉴定了 75 个在良性和恶性肿瘤亚型之间差异表达的基因。其中，与良性甲状腺肿瘤相比，恶性甲状腺肿瘤中有 33 个过表达，42 个过表达。使用最近邻分类对这些基因进行统计分析，显示预测恶性肿瘤的敏感性为 73%，特异性为 82%。实时逆转录 - 对其中 12 个基因进行 PCR 验证得到证实。对其中一个基因（高迁移率组 AT-hook 2）进行蛋白质印迹和免疫组织化学分析，进一步验证了微阵列和实时逆转录 - PCR 数据。结论：我们的结果表明，这 12 个基因可用于开发一组标记物来区分良性肿瘤和恶性肿瘤，从而作为解决与可疑甲状腺病变相关的临床问题的重要第一步。
Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as "suspicious" or "indeterminate." Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions.Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician.Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription - PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription - PCR data.Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.