Interrelation between lncRNA HOTAIR and EZH2 expression and progression free survival during endocrine treatment in breast cancer

HOTAIR and EZH2 have been identified to interact and to play a role in breast cancer development. In this retrospective clinical cohort study, HOTAIR lncRNA and EZH2 mRNA expression levels were analyzed to assess their combined value as a predictive marker in breast cancer. This retrospective study analyzed 1,465 patients with primary resectable breast cancer treated between 1979 and 1996. HOTAIR expression was measured in fresh frozen primary tumor tissue samples using qRT-PCR. Clinicopathological data were collected according to standardized criteria. Statistical analyses included non-parametric tests, logistic and Cox proportional hazards regression, and Kaplan-Meier curves and log-rank tests for survival outcomes (metastasis-free survival (MFS), progression-free survival (PFS), overall survival (OS)). Two-sided p-values < 0.05 were considered statistically significant. HOTAIR and EZH2 expression were both significantly associated with ER and HER2 status, and EZH2 also with age, histological features, and PR status. In 270 ER+/HER2- patients who received tamoxifen as first line treatment, higher expression of each HOTAIR and EZH2 were significantly associated with PFS, meanwhile, the combination of these two associated more strongly with PFS. In treatment-naïve lymph node-negative patients with ER+/HER2- tumors, higher HOTAIR expression was associated with worse MFS and OS with the tertile threshold. This study suggests that HOTAIR may have predictive value for tamoxifen resistance in ER+/HER2 − breast cancer, both independently and in combination with EZH2. Our findings further indicate that HOTAIR could potentially serve as a prognostic biomarker in this subtype.