Expression of serine peptidase inhibitor Kunitz type 1 in differentiated thyroid cancer
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.
KeywordsSerine protease inhibitor Hepatocyte growth factor Thyroid cancer Invasion
This work was supported by research grants from the Ministry of Science and Technology of Taiwan (MOST-104-2314-B-195-004-MY3) and MacKay Memorial Hospital (MMH-10712 and MMH-E-107-10).
Compliance with ethical standards
Institutional review board approval was obtained for the study, and the need for informed consent was waived.
Conflict of interest
The authors declare that they have no conflict of interest.
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