Long-Noncoding-RNA HOTAIR Upregulation is Associated with Poor Breast Cancer Outcome: A Systematic Review and Meta Analysis.

BACKGROUND:Breast cancer is the most frequent cancer among women worldwide with significant disproportionate mortality rates in developing countries. Although clinical management of breast cancer has been immensely improved, refinement in the prognostic and recurrent markers is still needed. Long non-coding RNAs (lncRNA) HOTAIR has recently been associated with poor outcome and is potentially used as a prognostic marker in breast cancer. METHODS:We comprehensively reviewed studies evaluating lncRNA HOTAIR in association with overall and disease-free survivals in breast cancers. Systematic searches were performed in Pubmed, ProQuest, ScienceDirect, Scopus, Google Scholar, Semantic Scholar, Springer, Nature, Sage Journals, and Wiley databases using combination keywords "long non-coding RNA," "lncRNA," "HOX transcript antisense RNA," "HOTAIR," "breast can-cer," "carcinoma mammae," "prognosis," and "survival." Risk of bias score was used to assess quality of studies, I2 test was conducted to assess heterogeneity. Meta-analysis was performed to compare HOTAIR expression with breast cancer survival rates using STATA v.17 software. RESULTS:Of the total 1,504 screened studies, seven studies were included in the meta-analysis involving 533 patients. High expression of HOTAIR was associated with poor survival rates (pooled HR: 1.69; 95%CI: 1.11-2.59; p=0.015), shorter overall survival (OS) (pooled HR: 1.33; 95%CI: 0.78-2.26; p=0.455), poor disease-free survival (DFS) (pooled HR: 2.40; 95%CI: 1.63-3.53; p<0.001), poor distant metastatic-free survival (MFS) (HR: 1.75; 95%CI: 1.13-2.71; p=0.012). In addition, overexpression of HOTAIR was associated with positive lymph node infiltration (pooled OR: 2.38; 95%CI: 0.53-10.69; p=0.26) and ductal type cancer (pooled OR: 3.27; 95%CI: 1.15-9.30; p=0.03). CONCLUSION:Upregulation of lncRNA HOTAIR is associated with worse DFS aand MFS that can potentially be used as a prognostic marker in breast cancer patients.