Association and clinical implication of the USP10 and MSH2 proteins in non-small cell lung cancer.

Abstract

Ubiquitin-specific protease 10 (USP10) is involved in a number of biological processes by stabilizing several proteins, which have been implicated in multiple stages of tumorigenesis and progression. Previous studies have indicated that USP10 stabilizes and deubiquitinates MutS homolog 2 (MSH2) in in vitro and in vivo models. The level of MSH2 protein has been positively correlated with that of the USP10 protein in a panel of lung cancer cell lines. Furthermore, depletion of USP10 in lung cancer cells causes decreased apoptosis and increased cell survival upon treatment with DNA-damaging agents. However, the expression and clinical implication of USP10 protein in lung cancer tissues is not clear. Additionally, whether the level of MSH2 protein is positively correlated with that of the USP10 protein in lung cancer tissues also remains unresolved. Therefore, USP10 protein expression was detected in 148 human non-small cell lung cancer (NSCLC) and 139 non-cancerous lung tissues using immunohistochemistry, whereas mRNA was investigated by Gene Expression Omnibus dataset and The Cancer Genome Atlas database analyses. It was identified that USP10 protein expression was significantly downregulated in NSCLC tissues compared with in normal lung tissues (P<0.05). However, no significant difference in USP10 mRNA expression between the two tissues was identified. In addition, a positive correlation was observed between the USP10 and MSH2 proteins in NSCLC tissues (P<0.05). However, the clinicopathological features and survival analysis indicated that the USP10 and MSH2 proteins were not associated with clinical features, including age, sex, tumor size, Tumor-Node-Metastasis stage and tumor cell differentiation, along with the prognosis of NSCLC. Collectively, these results suggest that downregulation of USP10 protein serves an important function in the tumorigenesis of NSCLC, and the level of USP10 protein is positively correlated with that of MSH2 protein in NSCLC tissues, which may indicate that USP10 also stabilizes the MSH2 protein in patients with lung cancer.