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DREAM基因mRNA水平在甲状腺肿瘤中的诊断效用

Diagnostic utility of DREAM gene mRNA levels in thyroid tumours.

作者信息

Batista Fernando A, Marcello Marjory A, Martins Mariana B, Peres Karina C, Cardoso Ulieme O, Silva Aline C D N, Bufalo Natassia E, Soares Fernando A, Silva Márcio J da, Assumpção Lígia V, Ward Laura S

机构信息

Laboratório de Genética Molecular do Câncer (Gemoca), Faculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brasil.

Departamento de Patologia, Hospital A.C. Camargo - Fundação Antonio Prudente, São Paulo, SP, Brasil.

出版信息

Arch Endocrinol Metab. 2018 Apr 5;62(2):205-211. doi: 10.20945/2359-3997000000028. Print 2018 Mar-Apr.

Abstract

OBJECTIVE

The transcriptional repressor DREAM is involved in thyroid-specific gene expression, thyroid enlargement and nodular development, but its clinical utility is still uncertain. In this study we aimed to investigate whether DREAM mRNA levels differ in different thyroid tumors and how this possible difference would allow the use of DREAM gene expression as molecular marker for diagnostic and/or prognosis purpose.

MATERIALS AND METHODS

We quantified DREAM gene mRNA levels and investigated its mutational status, relating its expression and genetic changes to diagnostic and prognostic features of 200 thyroid tumors, being 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesions [49 goiter and 50 follicular adenomas (FA)].

RESULTS

Levels of mRNA of DREAM gene were higher in benign (0.7909 ± 0.6274 AU) than in malignant (0.3373 ± 0.6274 AU) thyroid lesions (p < 0.0001). DREAM gene expression was able to identify malignancy with 66.7% sensitivity, 85.4% specificity, 84.2% positive predictive value (PPV), 68.7% negative predictive value (NPV), and 75.3% accuracy. DREAM mRNA levels were also useful distinguishing the follicular lesions FA and FVPTC with 70.2% sensitivity, 73.5% specificity, 78.5% PPV, 64.1% NPV, and 71.6% accuracy. However, DREAM gene expression was neither associated with clinical features of tumor aggressiveness, nor with recurrence or survival. Six different genetic changes in non-coding regions of DREAM gene were also found, not related to DREAM gene expression or tumor features.

CONCLUSION

We suggest that DREAM gene expression may help diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions; however, it is not useful as a prognostic marker.

摘要

目的

转录抑制因子DREAM参与甲状腺特异性基因表达、甲状腺肿大和结节形成,但它的临床应用价值仍不确定。在本研究中,我们旨在调查不同甲状腺肿瘤中DREAM mRNA水平是否存在差异,以及这种可能的差异是否能使DREAM基因表达作为诊断和/或预后的分子标志物。

材料与方法

我们对DREAM基因的mRNA水平进行定量,并研究其突变状态,将其表达和基因变化与200例甲状腺肿瘤的诊断和预后特征相关联,其中101例为恶性肿瘤[99例乳头状甲状腺癌(PTC)和2例间变性甲状腺癌],99例为良性甲状腺病变[49例甲状腺肿和50例滤泡性腺瘤(FA)]。

结果

DREAM基因的mRNA水平在良性甲状腺病变(0.7909±0.6274 AU)中高于恶性病变(0.3373±0.6274 AU)(p<0.0001)。DREAM基因表达能够以66.7%的敏感性、85.4%的特异性、84.2%的阳性预测值(PPV)、68.7%的阴性预测值(NPV)和75.3%的准确性识别恶性肿瘤。DREAM mRNA水平在区分滤泡性病变FA和FVPTC方面也很有用,敏感性为70.2%,特异性为73.5%,PPV为78.5%,NPV为64.1%,准确性为71.6%。然而,DREAM基因表达既与肿瘤侵袭性的临床特征无关,也与复发或生存无关。还发现了DREAM基因非编码区的六种不同基因变化,与DREAM基因表达或肿瘤特征无关。

结论

我们认为DREAM基因表达可能有助于诊断甲状腺结节,识别恶性肿瘤并对滤泡型甲状腺病变进行特征描述;然而,它作为预后标志物并无用处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a33/10118984/388155bdfb7c/2359-4292-aem-62-02-0205-gf01.jpg

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