Downregulated Expression of USP18 Is Associated with a Higher Recurrence Risk of Papillary Thyroid Carcinoma

Abstract

As a member of the deubiquitinating protease family, ubiquitin specific peptidase 18 (USP18) is well acknowledged for its roles in stabilizing downstream protein substrates and inhibiting type I interferon signaling. USP18 has been reported to exert distinct roles in different cancer types. However, its expression and function in papillary thyroid carcinoma (PTC) remain unknown. Here we collected 156 PTC patients and retrospectively retrieved their clinicopathological characteristics as well as their survival data. Among them, USP18 was hypoexpressed in 47 PTC samples (30.1%) and significantly correlated with oncogenic characteristics. According to univariate and multivariate analyses, low USP18 can act as an independent prognostic indicator for unfavorable progression-free survival of PTC patients. Ectopic overexpression and knockdown assays indicated that USP18 can negatively regulate the proliferation of PTC cell lines. The anti-tumor effect of USP18 was finally validated by xenografts results from nude mice. Taken together, PTC patients with low level of USP18 have worse survival compared to those possess high USP18 expression. Downregulated USP18 may be involved in the proliferation of PTC, and USP18 expression can serve as an independent survival predictor.