Abstract 4013: A 5-microRNA signature for prediction of prognosis and response to treatment in breast cancer

Abstract

Background: Studies have showed that MicroRNA (miRNA) plays an important role in cancer development and progression. We aimed to identify signature for predicting prognosis and response to treatment in breast cancer, which would help in making treatment decisions. Patients and Methods: We retrospectively analyzed miRNA expression profiles by a custom miRNA microarray in 422 archived paraffin-embedded breast cancers and 62 non-cancer breast tissues obtained from the Department of Pathology, Sun Yat-Sen University Cancer Center (Guangzhou, China). The patients with breast cancer were randomly divided into training set (211samples) and test set (211samples). The miRNA signature identified in training set was verified in test set and further confirmed by qRT-PCR method in another independent set including 161 breast cancers acquired from a different medical center. Results: A signature consisting of 36 miRNAs that were differently expressed between breast cancer and breast tissue was established in training set with an accuracy of 99.5% for distinguishing breast cancer from non-cancer breast tissues. The 36-miRNA signature was corroborated in test set with the same accuracy (99.5%). Then 5 miRNAs, which were significantly associated with patient survival, were constructed a signature and used to compute risk score in training set. Patients were divided into high- or low-risk group using the median risk score as a cutoff. Survival analysis showed that patients with high risk scores had poor prognosis in the training set, which was confirmed in the test set and independent set. This 5-miRNA signature was proven to be an independent prognostic predictor and could significantly improve the prognostic accuracy of TNM staging system. More important, the 5-miRNA signature could predict response to chemotherapy/radiotherapy in breast cancer patients after radical mastectomy. Conclusion: We identified a 36-miRNA signature that could distinguish breast cancer from non-tumor breast tissue, and a 5-miRNA signature that could predict survival and response to treatment, which could guide neoadjuvant therapy in breast cancer patients. The results in this study suggest that 5-miRNA signature will have a huge potential clinical implication in management of patients with breast cancer. Funding: National Natural Science Foundation of China/Joint Research Fund for Oversea Scholar (Grant No: 81228104 to Yibing Kang and Hui-Yun Wang). Citation Format: Jing-Ye Hu, Jun Tang, Wei Yi, Rong Deng, Mei-Yin Zhang, Guo-Liang Huang, Hui-Zhong Zhang, Jie-Hua He, X.F. Steven Zheng, Yibing Kang, Hui-Yun Wang. A 5-microRNA signature for prediction of prognosis and response to treatment in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4013. doi:10.1158/1538-7445.AM2015-4013