A PCR-based expression signature of malignancy in follicular thyroid tumors

A PCR-based expression signature of malignancy in follicular thyroid tumors
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DOI:
10.1677/erc-06-0023
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发表时间:
2007-06-01
影响因子:
3.9
通讯作者:
Zedenius, Jan
Zedenius, Jan
中科院分区:
医学2区
文献类型:
--
作者:
Foukakis, Theodoros;Gusnanto, Arief;Zedenius, Jan

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甲状腺滤泡状癌(FTC)的诊断,在没有转移,只能建立术后。此外,高风险的FTCs在诊断时往往无法识别。在这项研究中,我们的目的是确定转录标记的恶性和高风险的疾病在滤泡性甲状腺肿瘤。通过TaqMan定量RT-PCR方法,在一组75个滤泡性甲状腺肿瘤中测定26个潜在恶性肿瘤标志物的表达水平。逻辑回归分析(LRA)用于基因选择和诊断和预后算法的生成。基于五个基因(TERT、TFF 3、PPAR γ、CITED 1和EGR 2)表达水平的算法可以有效预测高危疾病,特异性为98.5%。在诊断时明显为良性或微创(MI)疾病但长期预后不良的所有4例病例中,转移潜力均可预测。此外,通过实施两个基因(TERT和TFF 3)产生了第二个模型,该模型能够区分腺瘤和事实上的癌。当在独立系列的非典型腺瘤(AFTA)和MI-FTC中测试该模型时,17个AFTA中的16个被分类为“良性”,而具有血管侵袭(有时称为“中度侵袭”)和/或大肿瘤尺寸的MI-FTC倾向于分类为“恶性”组。报告的模型可以为发展可靠的术前诊断和预后测试,可以指导治疗方法的滤泡性甲状腺肿瘤与不确定的细胞学的基础。
The diagnosis of follicular thyroid carcinoma (FTC) in the absence of metastasis can only be established postoperatively. Moreover, high-risk FTCs Eire often not identifiable at the time of diagnosis. In this study, we aimed to identify transcriptional markers of malignancy and high-risk disease in follicular thyroid tumors. The expression levels of 26 potential markers of malignancy were determined in a panel of 75 follicular thyroid tumors by a TaqMan quantitative RT-PCR approach. Logistic regression analysis (LRA) was used for gene selection and generation of diagnostic and prognostic algorithms. An algorithm based on the expression levels of five genes (TERT, TFF3, PPAR gamma, CITED1, and EGR2) could effectively predict high-risk disease with a specificity of 98.5%. The metastatic potential could be predicted in all four cases with apparently benign or minimally invasive (MI) disease at the time of diagnosis, but poor long-term outcome. In addition, a second model was produced by implementing two genes (TERT and TFF3), which was able to distinguish adenomas from de facto carcinomas. When this model was tested in an independent series of atypical adenomas (AFTA) and Ml-FTCs, 16 out of 17 AFTAs were classified as 'benign', while MI-FTCs with vascular invasion (sometimes referred to as 'moderately invasive') and/or large tumor size tended to classify in the 'malignant' group. The reported models can be the foundation for the development of reliable preoperative diagnostic and prognostic tests that can guide the therapeutic approach of follicular thyroid neoplasms with indeterminate cytology.