Endoplasmic Reticulum Chaperones Are Potential Active Factors in Thyroid Tumorigenesis

The study aimed to
evaluate the proteomic changes in benign follicular
adenoma versus malignant follicular variant of papillary thyroid carcinoma.
Tumor and nontumor adjacent samples were analyzed by liquid nanochromatography
mass spectrometry, and protein abundance was evaluated by label-free
quantification. Western blotting and quantitative real-time polymerase
chain reaction were used to validate and complement the mass spectrometry
data. The results demonstrated deregulated expression of four endoplasmic
reticulum chaperones (78 kDa glucose-regulated protein, endoplasmin,
calnexin, protein disulfide-isomerase A4), glutathione peroxidase
3 and thyroglobulin, all of them involved in thyroid hormone synthesis
pathway. The altered tissue abundance of endoplasmic reticulum chaperones
in thyroid cancer was correlated with serum expression levels. The
identified proteins significantly discriminate between adenoma and
carcinoma in both thyroid tissue and corresponding sera. Data are
available via ProteomeXchange with identifier PXD004322.

本研究旨在评估良性滤泡性腺瘤与恶性乳头状甲状腺癌滤泡亚型之间的蛋白质组学变化。研究通过液相纳米色谱-质谱联用技术对肿瘤及邻近非肿瘤样本进行分析，并采用无标记定量法评估蛋白丰度；同时利用蛋白质印迹法与实时定量聚合酶链反应对质谱数据进行验证与补充。结果显示，四种内质网伴侣蛋白（78 kDa葡萄糖调节蛋白、内质蛋白、钙连蛋白、蛋白质二硫键异构酶A4）、谷胱甘肽过氧化物酶3及甲状腺球蛋白的表达存在失调，上述蛋白均参与甲状腺激素合成通路。甲状腺癌组织中内质网伴侣蛋白的丰度改变与血清表达水平显著相关。所鉴定得到的蛋白可在甲状腺组织及对应血清样本中显著区分腺瘤与癌组织。相关数据可通过标识符为PXD004322的蛋白质组交换（ProteomeXchange）数据库获取。