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Meta-Analysis
. 2024 Apr 1;25(4):1169-1182.
doi: 10.31557/APJCP.2024.25.4.1169.

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

Suwardjo Suwardjo  1 , Kavi Gilang Permana  1 , Teguh Aryandono  1 , Didik Setyo Heriyanto  2 , Sumadi Lukman Anwar  1
Affiliations
Meta-Analysis

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

Suwardjo Suwardjo et al. Asian Pac J Cancer Prev. .

Abstract

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.

Keywords: HOTAIR; Prognosis; breast cancer; long non-coding RNA; survival.

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Conflict of interest statement

There is no conflict of interest in this research

Figures

Figure 1
Figure 1
Screening and Selection of Studies Included in Systematic Review
Figure 2
Figure 2
Comparison of HOTAIR Expression and the association with Survival Outcomes. Comparison of HOTAIR expression in breast cancer patients with (A) 5-years survival rates; (B) Overall survival; (C) Disease-free survival (DFS); (D) Metastasis-free survival (MFS). Hazard ratio (HR)
Figure 3
Figure 3
Subgroup Analyses of HOTAIR Expression and Survival According to the (A) country, (B) cut-off point of HOTAIR expression, C) 5-year survival, (D) methods of HOTAIR expression analyses, (E) primary samples
Figure 4
Figure 4
Comparison of HOTAIR Expression with Overall Survival According to (A) axillary lymph node status, (B) histological grades, C) histological type, (D) tumor size, (E) Her2-expression, (F) ER expression, and (G) PR expression
Figure 5
Figure 5
Funnel Plots for association between HOTAIR Expression and (A) Survival out-comes; (B) Overall survival; (C) Disease-free survival; (D) MFS; (E) Axillary lymph node status; (F) Histopathological grades; (G) Histological types; (H) Tumor Size; (I) HER2 expression; (J) ER expression; (K) PR expression
Figure 5
Figure 5
Funnel Plots for association between HOTAIR Expression (I) HER2 expression; (J) ER expression; (K) PR expression
Figure 6
Figure 6
Sensitivity Tests of Individual Study Effects on Pool HR for the Association of HOTAIR Upregulation and Overall Survival
Figure 7
Figure 7
Confirmation Analyses using TCGA Database using Kaplan-Meier Plots of Breast Cancer Overall Survival (A) and disease-free survival (B) according to the HOTAIR Expression
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