Evaluation of PACE4 isoforms as biomarkers in thyroid cancer.
Evaluation of PACE4 isoforms as biomarkers in thyroid cancer.
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评估PACE4同工型作为甲状腺癌的生物标志物。
DOI：
10.1186/s40463-018-0311-x
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发表时间：
2018-10-19
期刊：
影响因子：
--
通讯作者：
Day R
中科院分区：
文献类型：
--
作者：
Fradet L;Temmar R;Couture F;Belzile M;Fortier PH;Day R
迄今为止，当细针穿刺福尔斯落入Bethesda分类的“意义不明”类别时，没有单一的分子标记物被证明在临床上可用于区分恶性和良性甲状腺结节。PACE 4是前蛋白转化酶家族的一员，已显示通过形成称为PACE 4-altCT的致癌同种型在前列腺癌的发病机制中起主要作用。PACE 4亚型也被认为在其他癌症中发挥作用，包括甲状腺癌，但从未详细研究过。我们的目的是比较两种主要的PACE 4亚型在良性和恶性甲状腺结节中的组织化学分布，以确定它们作为区分性生物标志物的潜在用途。根据最终病理对接受甲状腺切除术的患者的甲状腺组织进行分类。使用针对两种PACE 4同种型（即全长PACE 4蛋白（PACE 4-FL）及其替代同种型（PACE 4-altCT））的C末端产生的两种先前验证的抗体，对相应的组织切片进行免疫染色。将结节与邻近的正常实质进行比较，并由头颈部病理学家将免疫染色评定为“低”或“高”。非病变甲状腺实质不表达PACE 4-FL（p = 0.002）。作为一组，恶性结节（n = 17）表达的PACE 4-FL显著高于良性结节（n = 24）（高免疫染色百分比：52.9% vs 4.2%; p = 0.001）。反过来，恶性结节中PACE 4-altCT的表达在统计学上低于相邻非病变实质中的表达（p = 0.014）。高PACE 4-FL免疫染色确定恶性肿瘤的特异性为95.8%（95%CI，78.9%至99.9%）。本研究支持之前描述的PACE 4-FL和PACE 4-altCT之间通过选择性剪接的关系。这也表明PACE 4-FL是一个有前途的甲状腺恶性肿瘤的生物标志物。它对恶性肿瘤的高特异性表达可能使其成为甲状腺癌的一个有趣的“规则”测试。目前正在设计进一步的前瞻性定量研究，以解决如何在临床环境中使用PACE 4亚型的测量。本研究未报告对人类参与者进行医疗干预的结果。尽管如此，它还是在ClinicalTrials.gov上注册，参考号为NCT 03160482。本文的在线版本（10.1186/s40463-018-0311-x）包含补充材料，可供授权用户使用。
To date, no single molecular marker has been demonstrated as clinically useful in differentiating malignant from benign thyroid nodules when a fine needle aspiration falls in the “unknown significance” categories of the Bethesda Classification. PACE4, a member of the proprotein convertase family of enzymes, has been shown to play a major role in the pathogenesis of prostate cancer, through the formation of an oncogenic isoform named PACE4-altCT. PACE4 isoforms have also been suggested to play a role in other cancers, including thyroid cancer, but have never been investigated in a detailed manner. Our objective is to compare the histochemical distribution of the two major PACE4 isoforms in benign and malignant thyroid nodules, in order to determine their potential usefulness as discriminatory biomarkers. Thyroid tissues of patients who underwent thyroidectomy were classified according to final pathology. Corresponding tissue sections were immunostained, using two previously validated antibodies raised against the C-terminal end of the two PACE4 isoforms, namely the full-length PACE4 protein (PACE4-FL) and its alternative isoform (PACE4-altCT). Nodules were compared with adjacent normal parenchyma and immunostaining was rated as “low” or “high” by a head and neck pathologist. Non-lesional thyroid parenchyma did not express PACE4-FL (p = 0.002). As a group, malignant (n = 17) nodules expressed PACE4-FL significantly more than benign (n = 24) nodules (percentage of high immunostaining: 52.9% vs 4.2%; p = 0.001). Reciprocally, there was a statistically lower expression of PACE4-altCT in malignant nodules than in adjacent non-lesional parenchyma (p = 0.014). The specificity of a high PACE4-FL immunostaining in determining malignancy was 95.8% (95% CI, 78.9% to 99.9%). This study supports the previously described relationship between PACE4-FL and PACE4-altCT through alternative splicing. It also suggests that PACE4-FL is a promising biomarker for thyroid malignancy. Its high specific expression for malignancy could make it an interesting “rule in” test for thyroid cancer. Further prospective, quantitative studies are currently being designed to address how measurements of PACE4 isoforms could be used in a clinical setting. This study does not report the results of a health care intervention on human participants. It was nonetheless registered on ClinicalTrials.gov under reference number NCT03160482. The online version of this article (10.1186/s40463-018-0311-x) contains supplementary material, which is available to authorized users.
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影响因子：
5.8
作者：
Nikiforova, MN;Lynch, RA;Nikiforov, YE
通讯作者：
Nikiforov, YE
DOI：
10.1111/j.1365-2362.2009.02162.x
发表时间：
2009-08-01
影响因子：
5.5
作者：
Guth, S.;Theune, U.;Bamberger, C. M.
通讯作者：
Bamberger, C. M.
影响因子：
3.3
作者：
Nour, N;Mayer, G;Seidah, NG
通讯作者：
Seidah, NG
前蛋白转化酶在卵巢癌细胞增殖和肿瘤进展中的影响：PACE4作为治疗靶点的见解。
影响因子：
5
作者：
Longuespee, Remi;Couture, Frederic;Levesque, Christine;Kwiatkowska, Anna;Desjardins, Roxane;Gagnon, Sandra;Vergara, Daniele;Maffia, Michelle;Fournier, Isabelle;Salzet, Michel;Day, Robert
通讯作者：
Day, Robert
影响因子：
3.9
作者：
SEIDAH, N;CHRETIEN, M;DAY, R
通讯作者：
DAY, R