The expression of Carbonic-anhydrase IX (CAIX) in thyroid cancer (TC) subtypes was determined and its role in cancer cell growth and tumor-initiating cells (TICs) investigated. Immunohistochemistry in 114 TC patients revealed that CAIX expression was increased in tumor specimens of papillary, follicular and anaplastic TCs compared to normal thyroid tissue. Clinicopathological data indicated that lymph node metastases were more frequent in patients with high CAIX expression. The Cancer Genome Atlas database analysis demonstrated that a strong CAIX-mRNA expression was associated with advanced tumor stages and poor survival in TCs. In TC cell lines, CAIX expression was elevated in tumorspheres compared to monolayer cultures and was associated with an increased expression of stemness markers. Genetic knockdown or pharmacological inhibition of CAIX suppressed cell proliferation and the TIC ability to form tumorspheres by an induction of apoptosis and cell-cycle arrest. These findings suggest CAIX as a potential prognostic marker and a therapeutic target for thyroid cancer.

测定了甲状腺癌 (TC) 亚型中碳酸酐酶 IX (CAIX) 的表达，并研究了其在癌细胞生长和肿瘤起始细胞 (TIC) 中的作用。114 名 TC 患者的免疫组织化学显示，与正常甲状腺组织相比，乳头状、滤泡状和间变性 TC 的肿瘤标本中 CAIX 表达增加。临床病理学数据表明，CAIX 高表达患者的淋巴结转移更为常见。癌症基因组图谱数据库分析表明，CAIX-mRNA 的强表达与晚期肿瘤阶段和 TC 的低存活率有关。在 TC 细胞系中，与单层培养物相比，CAIX 在肿瘤球中的表达升高，并且与干性标志物的表达增加有关。CAIX 的基因敲除或药理学抑制通过诱导细胞凋亡和细胞周期停滞来抑制细胞增殖和 TIC 形成肿瘤球的能力。这些发现表明 CAIX 是甲状腺癌的潜在预后标志物和治疗靶点。