Diagnostic value of LncRNAs for Postoperative Metastasis of Breast Cancer: A Nested Case-Control Study.

Abstract Background: Breast cancer is an aggressive tumor with no definitely identified prognostic biomarker for diagnosis. Studies have preliminarily found that lncRNAs are closely related to breast cancer metastasis, but, the significant clinical prediction of lncRNAs was remain unclear. In this study, we evaluated the diagnostic value of long non-coding RNA (lncRNA UCA1,CCAT2, ANCR) on postoperative metastasis of breast cancer as well as the possible mechanism involving the EMT.Methods: We investigated lncRNA ANCR, UCA1,CCAT2 are at high stake of breast cancer metastasis in a population-based nested case-control study. Metastasis cases were identified by clinical diagnostic criteria in approximately 103 cases in the Cancer Institute of Southwest Medical University during 2013-2020. Meanwhile, the control group (no-metastasis) was single out on the basis of the 1:1 pairing principle in this cohort (n=103, the matching condition was the surgery time within the same month, and the treatment plan both are modifed radical mastectomy ,age±3 years) The mRNA of lncRNA( UCA1,CCAT2, ANCR) expression was determined by Real-time PCR. By Western blot, the expression of E-cadherin, N-cadherin, and vimentin proteins was detected. The migration and invasion of transfected cells were determined by the Transwell assay.Results: lncRNA ANCR,UCA1,CCAT2 was significantly up-regulated in breast cancer cells and postoperative metastasis of breast cancer.CCAT2 (OR=1.024, 95% CI:1.010, 1.039), UCA1(OR=1.025, 95% CI: 1.011, 1.039),ANCR(OR=1.055, 95% CI:1.001, 1.111)was the risk factor for postoperative metastasis of breast cancer. Further more , By the ROC curve assay, we detect the optimal critical values of CCAT2, UCA1, ANCR , the risk of metastasis in the CCAT2 high expression group was 2.297 times that of the low expression group (OR=2.297, 95% CI:1.427 ~ 3.695, P< 0.05). The risk of metastasis in the UCA1 high expression group was 2.032 times that of the low expression group (OR=2.032, 95% CI 1.282 ~ 3.218, P<0.05). We further observed that lncRNA UCA1, CCAT2, ANCR was down-regulated in MDA-231 cells by 48 h of siRNA transfection. LncRNAs UCA1, CCAT2, ANCR silencing significantly decreased the migration and invasion cells, down-regulated N-cadherin, and up-regulated E-cadherin and vimentin in MDA-231 cells.Conclusions: Our data suggested that lncRNA CCAT2 ,UCA1,ANCR was a novel molecule involved in postoperative metastasis of breast cancer, which has predictive value in patients with breast cancer metastasis.