Park So-Hyun, Park Chan-Sung, Kim Young-Il, Nam-Goong Il-Seong, Kim Yon-Seon, Lee Jong-Cheol, Choi Jung-Il, Park Jeong-Woo, Kim Eun-Sook
Department of Endocrinology, Ulsan University Hospital, Ulsan, Korea E-mail :
Asian Pac J Cancer Prev. 2015;16(6):2447-51. doi: 10.7314/apjcp.2015.16.6.2447.
Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels.
Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively.
Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage.
Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.
人乳头状甲状腺癌(PTC)常与桥本甲状腺炎(HT)相关;二者共存可改善PTC的预后。骨桥蛋白是一种分泌型糖蛋白,在细胞存活、免疫及肿瘤进展中发挥作用,其表达与多种恶性肿瘤的不良预后及转移相关。骨桥蛋白过表达与PTC的侵袭性临床病理特征相关。淋巴结转移和肿瘤体积大与骨桥蛋白阳性呈正相关。本研究旨在:(1)证实人PTC样本中骨桥蛋白过表达;(2)比较有HT和无HT的PTC病例中骨桥蛋白的表达水平;(3)确定肿瘤侵袭性与骨桥蛋白表达水平之间的相关性。
采用酶联免疫吸附测定法评估45例PTC患者、22例合并HT的PTC患者及24名健康对照者血浆中的骨桥蛋白。分别通过逆转录-聚合酶链反应和蛋白质印迹法分析甲状腺组织中骨桥蛋白mRNA和蛋白质水平。
PTC患者血浆骨桥蛋白水平显著高于健康对照者。合并HT的PTC患者血浆骨桥蛋白、组织骨桥蛋白mRNA及组织骨桥蛋白蛋白水平显著低于单纯PTC患者。在疾病晚期病例中,合并HT的PTC患者骨桥蛋白mRNA和蛋白质表达水平低于单纯PTC患者。然而,骨桥蛋白表达水平与TNM分期无显著相关性。
合并HT的PTC患者血浆骨桥蛋白、组织骨桥蛋白mRNA及组织骨桥蛋白蛋白水平显著低于单纯PTC患者,提示HT通过对骨桥蛋白表达的负调控减弱PTC的侵袭性。