MO1-7-1Molecular and clinicopathological characterization of URST1 as a new biomarker and therapeutic target for breast cancer

Abstract Background Breast cancer is one of the most common causes of cancer death for women worldwide. Therefore, identification and evaluation of new prognostic biomarkers and therapeutic agents are required to overcome breast cancer. Methods 1) Selection of the candidate genes by gene expression profile database.2) Confirmation of high expression of candidate gene and its protein in breast cancer by qPCR andWestern-blotting. 3) Verification of clinicopathological significance of their protein expression by tissue microarray, 4) Evaluation of the cellular growth activity of gene products by siRNA experiments.During this process,we identify the biomarkers and therapeutic targets for breast cancer. Results We identified URST1 (Up-regulated Solid Tumor 1) as a candidate. Immunohistochemical analysis showed that URST1 was expressed in 195 of 257 (75%) breast cancers (69% in luminal type, 89% in HER2-positive cancer, and92% in TNBC) that had undergone curative surgery, whereas no staining was observed in adjacent normal breast tissues. URST1 expression was significantly related to poor clinical outcomes for breast cancer patients (P = 0.0126, Log-rank test) and multivariate analysis revealed that it was an independent prognostic factor. Knockdown of endogenous URST1 expression by siRNAs against URST1 or treatment with URST1 inhibitor significantly inhibited the breast cancer cell growth through cell cycle arrest at M phase and mitotic cell death as detected by flow cytometric analysis andcellular dynamicsanalysis of breast cancer cells using time-lapse microscopy. Conclusion URST1 appears to play an important role at the central spindle in mitosis of cancer cells. URST1 is a prognostic biomarker and therapeutic target for breast cancers.