Liu Chien-Liang, Yang Po-Sheng, Chien Ming-Nan, Chang Yuan-Ching, Lin Chi-Hsin, Cheng Shih-Ping
Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, 92, Section 2, Chung-Shan North Road, Taipei, 10449, Taiwan.
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
Histochem Cell Biol. 2018 Jun;149(6):635-644. doi: 10.1007/s00418-018-1660-2. Epub 2018 Mar 12.
SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61-68% of papillary thyroid cancer and 41-50% of follicular thyroid cancer. The overexpression diminished in anaplastic thyroid cancer. The SPINT1 expression in normal thyroid tissues and benign thyroid lesions was low. Furthermore, we noted that the SPINT1 expression was associated with extrathyroidal invasion, lymphovascular invasion, lymph node metastasis, advanced TNM stage, and a higher risk of recurrence in differentiated thyroid cancer. The results were in accordance with our analysis of The Cancer Genome Atlas data. In conclusion, an overexpression of SPINT1 appears to be associated with an invasive phenotype in differentiated thyroid cancer.
SPINT1，也称为HAI-1，是一种Kunitz型丝氨酸蛋白酶抑制剂，可抑制多种蛋白酶，包括肝细胞生长因子（HGF）激活剂和matriptase。已证明SPINT1在某些癌症类型中可调节HGF/MET激活。在本研究中，我们分析了微阵列数据集，发现SPINT1在分化型甲状腺癌中持续上调。使用组织微阵列和我们143例患者的独立样本研究了SPINT1蛋白表达。在61%-68%的乳头状甲状腺癌和41%-50%的滤泡状甲状腺癌中观察到SPINT1强表达。在未分化甲状腺癌中，这种过表达减少。正常甲状腺组织和良性甲状腺病变中的SPINT1表达较低。此外，我们注意到SPINT1表达与分化型甲状腺癌的甲状腺外侵犯、淋巴管侵犯、淋巴结转移、晚期TNM分期以及更高的复发风险相关。结果与我们对癌症基因组图谱数据的分析一致。总之，SPINT1的过表达似乎与分化型甲状腺癌的侵袭性表型相关。
