Abstract P5-07-05: LOC283299 suppress the lymphnode metastatic cascade in breast cancer patients

Abstract

Abstract Background Long non-coding RNAs (lncRNAs) have been proved to play an essential role in cancer metastasis. The accuracy of intraoperative assessment of lymph nodes metastasis need to be improved. In this study, we aimed to define the lncRNA biomarker ectopic expressed in breast cancer patients' metastatic lymph nodes, and to explore the potential molecular mechanisms. Experimental Design RNA-seq analyses in 3 paired breast cancer patients' primary tumor and metastatic lymph node was used as training set to determine differentially expressed lncRNAs that may be associated with lymph node metastasis. The other 40 patients were analyzed as validation set to test the accuracy of lncRNAs identification by quantitative real-time PCR. The correlation between LOC283299 expression level and prognosis in other 282 breast cancer patients was confirmed. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of LncRNA-dependent lymph node metastases and prognosis. Results RNA-seq analyses in the training set revealed significant correlation between high expression level of LOC283299 and lower lymph node metastasis potential in breast cancer patients. We further validated that the expression level of LOC283299 was significantly higher in tumor primary tissue than that in paired metastatic lymph node (P=0.0245), and higher LOC283299 expression level was markedly associated with good metastasis-free survival in breast cancer patients (P=0.04). In breast cancer cell lines, CRISPR-on overexpression of LOC283299 inhibited proliferation, migration, invasion, and metastases both in vivo and in vitro. shRNA knockdown LOC283299 promotes the ability of tumor proliferation and metastasis. The molecular mechanisms by which LOC283299 as metastasis-suppressing lncRNAs regulates recurrence and metastasis may involve regulation of epithelial to mesenchymal transition (EMT), cellular invasion and microenvironment in breast cancer cells. Conclusion Our study revealed a strong correlation between LOC283299 expression and lymph node metastases in breast cancers. High level of LOC283299 was associated with better metastasis-free survival. The changed metastasis phenotype may be mediated by the interaction of LOC283299 and breast cancer cells. Therefore, LOC283299 may represent a potential predictive biomarker for early lymph node metastasis in breast cancer. Citation Format: Guo R, Xue J, Su Y, Xiu B, Ji W, Chi Y, Wu J. LOC283299 suppress the lymphnode metastatic cascade in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-05.