Abstract P4-04-16: Long non-coding RNA DSCAM-AS1 regulates G1/S cell cycle transition and is an independent poor prognosis factor in luminal breast cancer with endocrine therapy

Abstract

Abstract While an increasing number of long non-coding RNAs (lncRNAs) have been revealed to play fundamental roles in tumorigenesis and progression of triple negative breast cancer (TNBC), lncRNA studies on luminal breast cancer, which accounting for two thirds of all breast tumor, are still rare. DSCAM-AS1 is the first and only intensively studied lncRNA with high specific expression in luminal breast cancer, directly regulated by estrogen receptor α (ERα), and playing vital roles in tumor proliferation, invasion and tamoxifen resistance. However, the detailed function of DSCAM-AS1 in tumor progression and its clinical significance are still not clear. In this study, we revealed that DSCAM-AS1 regulates cell proliferation and colony formation by inducing cell cycle G1/S transition. RNA-seq analysis demonstrated that DSCAM-AS1 participates in crucial biological processions including DNA replication, cell cycle G1/S phase transition, sister chromatid cohesion, chromosome segregation, protein localization to chromosome and DNA recombination. For clinical analysis, a total of 399 luminal breast cancer patients were enrolled, with median follow-up time of 58.91 months (Interquartiles range, 42.90-70.65) and 72 events. The median age was 48 years (Interquartiles range, 42-58). All the patients have received tumor resection. 165 (41.35%) patients have received radiotherapy and 342 (85.71%) patients were treated with chemotherapy. With a cut-off value of 13.05 (ΔCT value), DSCAM-AS1 were high expressed in 239 patients, and low expressed in 160 patients. In the total cohort, univariate survival analysis revealed that characteristics including tumor size (p=0.005), grade (p=0.004), positive lymph nodes number (p<0.0001) and ki-67 (p=0.012) were correlated with prognosis. High expression of DSCAM-AS1 was inclined to shorter disease free survival (DFS), although no statistic difference has been reached (p=0.061). DSCAM-AS1 was not an independent factor for the total cohort (HR, 1.46; 95% CI, 0.86-2.46; p=0.16). Of all the 399 patients, 309 (77.44%) have received more than one year endocrine therapy and were included into the endocrine therapy group. In the endocrine therapy group, patients with high DSCAM-AS1 expression level had shorter DFS in the univariate analysis. In the multivariate analysis, DSCAM-AS1 (HR, 2.22; 95%CI, 1.16-4.23; p=0.016) together with grade (HR, 1.88; 95%CI, 1.11-3.21; p=0.02) and positive lymph nodes number (HR, 2.04; 95%CI, 1.47-2.84; p<0.0001) were independent prognosis factors. In conclusion, DSCAM-AS1 is a prognostic factor, although no statistical significance, in patients with luminal breast cancer. In luminal breast cancer patients with endocrine therapy, high expression of DSCAM-AS1 acts as a poor independent factor to affect patients' DFS. DSCAM-AS1 is a promising clinical therapy target to prolong luminal breast cancer patients' survival, together with endocrine therapy. Citation Format: Zhou P, Sun W, Shao Z-M. Long non-coding RNA DSCAM-AS1 regulates G1/S cell cycle transition and is an independent poor prognosis factor in luminal breast cancer with endocrine therapy [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 P4-04-16.