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甲状腺癌中与糖酵解相关的蛋白表达

Glycolysis-related protein expression in thyroid cancer.

作者信息

Nahm Ji Hae, Kim Hye Min, Koo Ja Seung

机构信息

Severance Hospital and Department of Pathology, College of Medicine, Yonsei University, Seoul, South Korea.

出版信息

Tumour Biol. 2017 Mar;39(3):1010428317695922. doi: 10.1177/1010428317695922.

Abstract

We aimed to demonstrate the differences in the expression of glucose metabolism-related proteins according to the thyroid cancer subtypes and investigate the implications of these differences. A total of 566 thyroid cancer patients, including 342 cases of papillary thyroid carcinoma, 112 cases of follicular carcinoma, 70 cases of medullary carcinoma, 23 cases of poorly differentiated carcinoma, 19 cases of anaplastic carcinoma, and 152 cases of follicular adenoma, were enrolled in the study. Immunohistochemical staining for glucose transporter 1, hexokinase II, carbonic anhydrase IX, and monocarbonylate transporter 4 was performed, and the relationship between immunoreactivity and clinicopathologic parameters was analyzed. Glucose transporter 1 and tumoral monocarbonylate transporter 4 expression levels were shown to be the highest in anaplastic carcinoma, and medullary carcinoma showed the highest carbonic anhydrase IX and lowest hexokinase II levels compared with other subtypes. Stromal expression of monocarbonylate transporter 4 was observed in papillary thyroid carcinoma and anaplastic carcinoma samples. Conventional papillary thyroid carcinoma tumors expressed higher levels of glucose transporter 1, and tumoral and stromal monocarbonylate transporter 4, than the follicular variant, which showed a higher expression of carbonic anhydrase IX. Papillary thyroid carcinoma samples with BRAF V600E mutation were shown to have higher glucose transporter 1, hexokinase II, carbonic anhydrase IX, and tumoral monocarbonylate transporter 4 expression levels. Univariate analysis showed that papillary thyroid carcinoma cases with glucose transporter 1 positivity had shorter overall survival, patients with medullary carcinoma and hexokinase II positivity were shown to have a shorter disease-free survival and overall survival, and tumoral monocarbonylate transporter 4 positivity was associated with shorter overall survival compared with papillary thyroid carcinoma patients with negativity for each marker. Disease-free survival and overall survival of patients with poorly differentiated carcinoma were shown to be significantly decreased when glucose transporter 1 and tumoral monocarbonylate transporter 4 are expressed. We demonstrated that the expression levels of glycolysis-related proteins differ between thyroid cancer subtypes and are correlated with poorer prognosis, depending on the subtype.

摘要

我们旨在根据甲状腺癌亚型展示葡萄糖代谢相关蛋白表达的差异,并研究这些差异的意义。本研究共纳入566例甲状腺癌患者,包括342例乳头状甲状腺癌、112例滤泡状癌、70例髓样癌、23例低分化癌、19例未分化癌以及152例滤泡性腺瘤。对葡萄糖转运蛋白1、己糖激酶II、碳酸酐酶IX和单羧酸转运蛋白4进行免疫组织化学染色,并分析免疫反应性与临床病理参数之间的关系。结果显示,未分化癌中葡萄糖转运蛋白1和肿瘤单羧酸转运蛋白4的表达水平最高,与其他亚型相比,髓样癌中碳酸酐酶IX水平最高,己糖激酶II水平最低。在乳头状甲状腺癌和未分化癌样本中观察到单羧酸转运蛋白4的基质表达。与滤泡状变体相比,传统乳头状甲状腺癌肿瘤中葡萄糖转运蛋白1、肿瘤和基质单羧酸转运蛋白4的表达水平更高,而滤泡状变体中碳酸酐酶IX的表达更高。具有BRAF V600E突变的乳头状甲状腺癌样本显示出更高的葡萄糖转运蛋白1、己糖激酶II、碳酸酐酶IX和肿瘤单羧酸转运蛋白4表达水平。单因素分析显示,葡萄糖转运蛋白1阳性的乳头状甲状腺癌患者总生存期较短,髓样癌且己糖激酶II阳性的患者无病生存期和总生存期较短,与各标志物阴性的乳头状甲状腺癌患者相比,肿瘤单羧酸转运蛋白4阳性与总生存期较短相关。当葡萄糖转运蛋白1和肿瘤单羧酸转运蛋白4表达时,低分化癌患者的无病生存期和总生存期显著降低。我们证明,糖酵解相关蛋白的表达水平在甲状腺癌亚型之间存在差异,并且根据亚型不同与较差的预后相关。

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