Purpose

Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet.

Methods

We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a “Surgical series” of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a “Cytological series” of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot.

Results

We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology.

Conclusion

These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

中文翻译：

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妊娠相关血浆蛋白 A mRNA 表达作为分化型甲状腺癌的标志物：“手术”和“细胞学”系列的结果

目的

妊娠相关血浆蛋白 A (PAPPA) 是一种金属蛋白酶，最初因其在妊娠期间的作用而被描述。PAPPA 通过降解 IGF 结合蛋白 4 (IGFBP4) 来调节 IGF 配体 1 (IGF1) 的生物利用度。在 IGFBP4 裂解后，游离 IGF1 能够结合 IGF1 受体 (IGF1R)，从而触发下游信号传导。最近，PAPPA 表达与几种癌症的发展有关。目前还没有关于甲状腺癌的数据发表。

方法

我们评估了 PAPPA、胰岛素样生长因子 (IGF1)、IGF1 受体 (IGF1R) 和 IGF 结合蛋白 4 (IGFBP4) mRNA 表达水平在 94 个甲状腺结节（64 个癌症、16 个滤泡性腺瘤和 14 个增生）的“手术系列”中结节）和“细胞学系列”中 74 名接受细针抽吸细胞学检查 (FNAC) 的患者的 80 个结节。在组织中，还通过蛋白质印迹评估了 PAPPA。

结果

我们发现甲状腺癌标本中 PAPPA 在 mRNA 和蛋白质水平上的表达增加，腺瘤和增生结节的表达与正常组织相似。当应用于甲状腺细胞学时，PAPPA 表达能够区分良性和恶性结节，有助于结节的术前分类。我们计算了一个具有良好特异性 (91%) 的截止值，当与分子生物学结合时达到 100%。

结论

这些结果表明，PAPPA 可以代表分化型甲状腺癌的有希望的诊断标志物。