Srisomsap Chantragan, Subhasitanont Pantipa, Otto Albrecht, Mueller Eva-Christina, Punyarit Phaibul, Wittmann-Liebold Brigitte, Svasti Jisnuson
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
Proteomics. 2002 Jun;2(6):706-12. doi: 10.1002/1615-9861(200206)2:6<706::AID-PROT706>3.0.CO;2-E.
Nodular or multinodular goiter is the most common non-neoplastic thyroid disease and may be difficult to distinguish from true neoplastic thyroid diseases using microscopic criteria. We have used two-dimensional gel electrophoresis to study the protein patterns of thyroid tissues including normal thyroid, multinodular goiter, diffuse hyperplasia, follicular adenoma, follicular carcinoma and papillary carcinoma. Specific proteins, in the region of molecular mass 15-30 kDa and isoelectric point 4.5-6.5, were identified by electrospray tandem mass spectrometry and protein sequencing. The most distinctive protein found is cathepsin B, which could be detected as four spots, with differential expression in different thyroid diseases. In particular, two of these cathepsin B spots CB2 and CB3 are strongly up-regulated in neoplastic diseases, compared to non-neoplastic diseases. In addition, overexpression of ATP synthase D chain and prohibitin were observed in papillary carcinoma, which should allow it to be differentiated from follicular carcinoma. Changes in expression of other proteins were also observed in disease states compared to normal tissues, namely translationally controlled tumor protein, thioredoxin peroxidase 1, glutathione-S-transferase P, DJ-1 protein, superoxide dismutase (Cu, Zn), and heat shock protein 27, but these changes are less characteristic, so they do not allow the differentiation between neoplastic and non-neoplastic tissues. Thus, the proteomic approach is a useful diagnostic tool for studying diseases involving the thyroid nodule.
结节性或多结节性甲状腺肿是最常见的非肿瘤性甲状腺疾病，使用显微镜标准可能难以与真正的肿瘤性甲状腺疾病区分开来。我们使用二维凝胶电泳研究了包括正常甲状腺、多结节性甲状腺肿、弥漫性增生、滤泡性腺瘤、滤泡性癌和乳头状癌在内的甲状腺组织的蛋白质模式。通过电喷雾串联质谱和蛋白质测序鉴定了分子量在15 - 30 kDa之间、等电点在4.5 - 6.5之间的特定蛋白质。发现的最具特色的蛋白质是组织蛋白酶B，它可以被检测为四个斑点，在不同的甲状腺疾病中表达存在差异。特别是，与非肿瘤性疾病相比，这些组织蛋白酶B斑点中的两个，即CB2和CB3，在肿瘤性疾病中强烈上调。此外，在乳头状癌中观察到ATP合酶D链和抑制素的过表达，这应该有助于将其与滤泡性癌区分开来。与正常组织相比，在疾病状态下还观察到其他蛋白质表达的变化，即翻译控制肿瘤蛋白、硫氧还蛋白过氧化物酶1、谷胱甘肽 - S - 转移酶P、DJ - 1蛋白、超氧化物歧化酶（铜，锌）和热休克蛋白27，但这些变化的特征性较差，因此它们无法区分肿瘤性和非肿瘤性组织。因此，蛋白质组学方法是研究涉及甲状腺结节疾病的一种有用的诊断工具。
