Characterization of URST1 as a prognostic biomarker and therapeutic target for lung and oral cancers.

Abstract

e14057 Background:Lung cancer and oral cavity cancer belong to aerodigestive cancers whose clinical outcome after multimodal therapy remains poor. Methods:To identify new biomarkers and therapeutic targets for lung and oral cancers, we screened genes using our original gene expression profile database for various solid cancers, and characterized clinical and oncogenic values of up-regulated in solid tumor 1 (URST1) protein as a candidate. Results: URST1 was highly expressed in the most of lung or oral cancer cell lines and tumor tissues, but was hardly detected in normal lung or oral epithelial cells and tissues as detected by real-time PCR and western blot analyses. Immunocytochemical analysis revealed that URST1 was mainly localized in the nucleus and cytoplasm of lung or oral cancer cell lines. Immunohistochemical analysis using tissue microarray showed that positive staining of URST1 was observed in 231 of 358 (64.5%) lung cancers, but not in normal lung, and it was significantly associated with poor prognosis after curative surgery. In addition, URST1 was expressed in 64 of 96 (66.7%) oral cancers, but not in oral mucosa, and it was significantly correlated with poor clinical outocome after surgery. Multivariate analysis confirmed that URST1 expression was an independent prognostic factor for oral cancer. Suppression of URST1 expression by siRNA or treatment with synthesized inhibitor specific for URST1 activity inhibited mitosis and growth of lung or oral cancer cell lines. Conclusions:URST1 is likely to be a prognostic biomarker and therapeutic target for aerodigestive cancers such as lung and oral cancers.