PVALB, a New Hurthle Adenoma Diagnostic Marker Identified through Gene Expression
PVALB, a New Hurthle Adenoma Diagnostic Marker Identified through Gene Expression
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DOI：
10.1210/jc.2010-1318
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发表时间：
2011-01-01
影响因子：
5.8
通讯作者：
Riggins, Gregory J.
中科院分区：
文献类型：
--
作者：
Cerutti, Janete M.;Oler, Gisele;Riggins, Gregory J.
背景：需要一种更好的方法来准确识别恶性甲状腺结节并将其与良性肿瘤区分开来。我们以前确定了检测甲状腺恶性肿瘤的标志物，敏感性估计为或接近100%。一个挥之不去的问题，这些标志物是假阳性发生与Hurthle细胞腺瘤（HCA），降低测试specificity.Methods：要找到准确的诊断标志物，我们剖析了深入的HCA和Hurthle细胞癌（HCC）的成绩单。从1146个差异表达基因中，18个转录本特异性表达HCA进行了测试，在广泛的甲状腺肿瘤（n = 76）的定量PCR。采用受试者工作特征（ROC）计算敏感性和特异性。通过免疫组织化学在一组独立的甲状腺肿瘤（n = 82）中进一步验证了所选标记物。为了确定能产生最佳诊断准确性的基因组，将这些标记物与我们先前鉴定的标记物相结合进行测试。结果：18个基因中有17个基于平均相对表达水平显示出统计学显著性（P < 0.05）。KLK 1（敏感性= 0.97）和PVALB（敏感性= 0.94）是最佳候选标志物。PVALB和C1 orf 24的组合增加特异性到> 97%，并保持检测cancer.Conclusion的敏感性：我们确定了肿瘤标记物，可用于更准确的术前诊断甲状腺结节和术后诊断甲状腺癌的肿瘤切片。这种改进的测试将帮助医生迅速将治疗重点放在真正的恶性肿瘤上，避免对良性肿瘤进行不必要的治疗，同时改善医疗保健并降低成本。（临床内分泌代谢杂志96：E151-E160，2011）
Context: A better means to accurately identify malignant thyroid nodules and to distinguish them from benign tumors is needed. We previously identified markers for detecting thyroid malignancy, with sensitivity estimated at or close to 100%. One lingering problem with these markers was that false positives occurred with Hurthle cell adenomas (HCA) which lowered test specificity.Methods: To locate accurate diagnostic markers, we profiled in depth the transcripts of a HCA and a Hurthle cell carcinoma (HCC). From 1146 differentially expressed genes, 18 transcripts specifically expressed in HCA were tested by quantitative PCR in a wide range of thyroid tumors (n = 76). Sensibility and specificity were calculated using receiver operating characteristic (ROC). Selected markers were further validated in an independent set of thyroid tumors (n = 82) by immunohistochemistry. To define the panel that would yield best diagnostic accuracy, these markers were tested in combination with our previous identified markers.Results: Seventeen of the 18 genes showed statistical significance based on a mean relative level of expression (P < 0.05). KLK1 (sensitivity = 0.97) and PVALB (sensitivity = 0.94) were the best candidate markers. The combination of PVALB and C1orf24 increased specificity to > 97% and maintained sensitivity for detection of carcinoma.Conclusion: We identified tumor markers that can be used in combination for a more accurate preoperative diagnosis of thyroid nodules and for postoperative diagnosis of thyroid carcinoma in tumor sections. This improved test would help physicians rapidly focus treatment on true malignancies and avoid unnecessary treatment of benign tumors, simultaneously improving medical care and reducing costs. (J Clin Endocrinol Metab 96: E151-E160, 2011)