Pezzani Raffaele, Bertazza Loris, Cavedon Elisabetta, Censi Simona, Manso Jacopo, Watutantrige-Fernando Sara, Pennelli Gianmaria, Galuppini Francesca, Barollo Susi, Mian Caterina
Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Via Ospedale 105, Padova 35128, Italy.
Associazione Italiana per la Ricerca Oncologica di Base (AIROB), Padova, Italy.
Int J Endocrinol. 2019 Feb 18;2019:9421079. doi: 10.1155/2019/9421079. eCollection 2019.
Medullary thyroid cancer (MTC) is a rare neuroendocrine-derived malignancy. It is represented by sporadic and familiar forms, and both can have oncogene mutations. Numerous markers can be used to define MTC; however, none is generally approved for predicting the outcome of sporadic MTC.
The aim of this work was to analyze PTTG1/securin and Aurora kinase A expressions in MTC patients, both at the gene and protein levels, and to define their prognostic role in MTC assessing their association with lab and clinical parameters.
Seventy-one sporadic MTC human samples were analyzed for mutations and by qPCR for and (Aurora kinase A) expression. Ki-67 levels and western blot reactivity for PTTG1 and Aurora kinase A were also determined in a selected cohort of patients.
somatic mutations were found in 48% of the patients (34/71). expression was statistically different among the groups with or without regional lymph node metastasis ( < 0.0001) and advanced stage disease ( < 0.01). and expressions were statistically higher than those of controls ( = 0.01 and < 0.002, respectively). expression and Ki-67 levels were statistically different among the groups with remitted or persistent disease ( < 0.05 and < 0.01, respectively). We found a significant correlation between the expressions of and ( < 0.0002, = 0.5298) and between the expressions of and Ki-67 ( = 0.01). Ki-67 levels were statistically different among the groups with or without metastatic lymph nodes ( = 0.01) or distant metastases ( = 0.003).
The presence of an altered expression of and is a negative prognostic factor associated with a more aggressive course of disease, such as an advanced stage or disease persistence. It emerges as a cell cycle process mediated by the 2 factors, in addition to the RET pathway, which can be altered in MTC patients.
甲状腺髓样癌（MTC）是一种罕见的神经内分泌源性恶性肿瘤。它有散发性和家族性两种形式，两者都可能发生癌基因突变。许多标志物可用于定义MTC；然而，目前尚无一种被普遍认可用于预测散发性MTC的预后。
本研究旨在分析MTC患者中PTTG1/分离酶和极光激酶A在基因和蛋白水平的表达，并通过评估它们与实验室及临床参数的相关性来确定其在MTC中的预后作用。
对71例散发性MTC患者的样本进行基因突变分析，并通过qPCR检测PTTG1和极光激酶A的表达。在部分选定患者中还测定了Ki-67水平以及PTTG1和极光激酶A的蛋白质免疫印迹反应性。
48%（34/71）的患者检测到体细胞突变。PTTG1的表达在有无区域淋巴结转移组（P<0.0001）和疾病晚期组（P<0.01）之间存在统计学差异。PTTG1和极光激酶A的表达均显著高于对照组（分别为P = 0.01和P<0.002）。PTTG1表达和Ki-67水平在疾病缓解或持续组之间存在统计学差异（分别为P<0.05和P<0.01）。我们发现PTTG1和极光激酶A的表达之间存在显著相关性（P<0.0002，r = 0.5298），PTTG1和Ki-67的表达之间也存在显著相关性（P = 0.01）。有无转移性淋巴结组（P = 0.01）或远处转移组（P = 0.003）之间的Ki-67水平存在统计学差异。
PTTG1和极光激酶A表达改变的存在是与疾病更具侵袭性病程相关的不良预后因素，如疾病晚期或疾病持续。除了RET途径外，它还表现为由这两种因子介导的细胞周期过程，这在MTC患者中可能会发生改变。
