Abstract

Abstract This study aims to identify novel biomarkers and therapeutic targets for lung cancer. Our strategies are as follows: i) Identification of up-regulated genes in lung cancers by gene expression profile analysis, ii) Validation of clinicopathological importance of their protein expression using tissue microarray, iii) Examination of their effect on cancer cell proliferation/survival by siRNAs and/or small molecules. During this process, we identified up-regulated in solid tumor 1 (URST1). Immunohistochemical analysis of URST1 expression revealed that URST1 expression was observed in the majority of non-small cell lung cancers (NSCLCs) and SCLCs. Strong positivity of URST1 staining was correlated with tumor size and lymph node metastasis and it was significantly associated with poor prognosis for NSCLC patients. Multivariate analysis showed that strong expression of URST1 was an independent prognostic factor for NSCLCs that had undergone curative surgery. Inhibition of URST1 expression by siRNAs for URST1 suppressed the growth and invasive ability of lung cancer cells. Treatment of lung cancer cells with selective inhibitors for URST1 significantly suppressed the cell growth partly through G2/M arrest and subsequent cell death. Downstream targets of URST1 were identified by microarray analysis using lung cancer cells transfected with siRNAs for URST1. Targeting URST1 is likely to be an effective diagnostic and therapeutic approach for lung cancer. Citation Format: Atsushi Takano, Yohei Miyagi, Yataro Daigo. Identification of URST1 as a prognostic biomarker and therapeutic target for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1214.

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