Characterization of URST1 as a prognostic marker and therapeutic target for lung cancer.

Abstract

e21000 Background: The improved understanding of cancer-specific oncoproteins could lead to the development of novel biomarkers or therapeutic targets for lung cancers. Methods: We screened oncoproteins as follows: i) Identification of up-regulated genes in lung cancers by cDNA microarray, ii) Validation of clinicopathologic importance of their gene product by tissue microarray, iii) Examination of the growth of cancer cells after transfection of their siRNA or expression vector, iv) Screening of their signal pathways. Results: We identified up-regulated in solid tumor 1 (URST1) as a candidate. Immunohistochemical staining of URST1 showed that URST1 expression was observed in 231 (64.5%) of 358 non-small cell lung cancers (NSCLC) and 11 (84.6%) of 13 small cell lung cancers. High level of URST1 expression was associated with poor prognosis for NSCLC patients ( P = 0.0003). Multivariate analysis confirmed that strong URST1 expression was an independent prognostic factor for NSCLC patients that had undergone radical surgery. Knockdown of URST1expression by siRNAs against URST1 significantly suppressed the growth of lung cancer cells, and also inhibited the cell invasive ability. Treatment of lung cancer cells with small molecule inhibitor against URST1 suppressed the cell growth partly through G2/M arrest and cell death. In contrast, enforced expression of URST1 significantly promoted lung cancer cell growth. Microarray analysis coupled with siRNAs for URST1 suggested various URST1 related oncogenic pathways in lung cancer cells. Conclusions: URST1 could play an essential role in malignant potential of lung cancer and it might be useful as a prognostic biomarker and therapeutic target molecule for lung cancer.