Prognostic role of HOTAIR in four estrogen-dependent malignant tumors: a meta-analysis

Background: HOX transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA transcribed from the antisense strand of the HOXC gene locus, has been shown to be overexpressed in various carcinomas and is thought to be an indicator of poor prognosis. Recently, HOTAIR was found to be an estrogen-responsive gene. We therefore conducted a meta-analysis to systematically summarize and clarify the association between HOTAIR expression and prognosis in the four main estrogen-dependent tumors. Methods: A systematic search of studies that examined the association and prognostic impact of HOTAIR in four of the main estrogen-dependent tumors was conducted in PubMed and Embase. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to pool the effect size. Results: A total of 1,200 patients from eight eligible studies were included. The current study found an association between HOTAIR expression and overall survival (OS) in four estrogen-dependent tumor types (HR, 1.99; 95% CI: 1.02-3.90; P-Heterogeneity= 0.001). Subgroup analyses indicated that high HOTAIR expression appeared to be a potential prognostic biomarker in non-breast cancer patients (HR, 2.72; 95% CI: 1.65-4.48). There was also an increased risk in Asian populations (HR, 2.55; 95% CI: 1.62-4.00) compared with Caucasian populations (HR, 1.19; 95% CI: 0.16-8.83) and in patients without preoperative treatment (HR, 2.55; 95% CI: 1.62-4.00) compared with patients with preoperative treatment (HR, 1.19; 95% CI: 0.16-8.83). In addition, the HRs of patients with high HOTAIR expression for metastasis-free survival (MFS), relapse-free survival (RFS), and disease-free survival (DFS) were 2.30 (P=0.120), 1.39 (P=0.000), and 2.53 (P=0.714), respectively, but there were insufficient data to fully confirm these associations. Conclusion: HOTAIR may be a predictor of poor prognosis in four of the main estrogen-dependent tumors, especially in cervical, ovarian, and endometrial cancer patients without preoperative treatment in Asian populations. It is important to note that the prognostic value of HOTAIR in MFS, RFS, and DFS should be interpreted with caution due to the limited sample size and sample heterogeneity. Well-designed and larger-scale studies are needed to validate our findings.