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Meta-Analysis
. 2018 Sep;171(2):261-271.
doi: 10.1007/s10549-018-4839-2. Epub 2018 May 29.

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Zhanwei Wang  1 , Dionyssios Katsaros  2 , Nicoletta Biglia  3 , Yi Shen  1 , Yuanyuan Fu  1   4 , Lenora W M Loo  1 , Wei Jia  1 , Yuki Obata  5 , Herbert Yu  6
Affiliations
Meta-Analysis

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Zhanwei Wang et al. Breast Cancer Res Treat. 2018 Sep.

Abstract

Purpose: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a prognostic marker for the metastasis of early-stage non-small cell lung cancer (NSCLCs). We studied MALAT1 expression in breast cancer in relation to disease features and patient survival.

Methods: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure MALAT1 expression in tumor samples of 509 breast cancer patients. Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between MALAT1 expression and breast cancer survival using the Cox proportional hazards regression model, and the analysis was adjusted for age at surgery, tumor grade, disease stage, and hormone receptor status. Meta-analysis of multiple microarray datasets from online databases and our own study was performed to evaluate the association of MALAT1 with breast cancer survival.

Results: Patients with low-grade or ER-positive tumors had higher expression of MALAT1 compared to those with high-grade (p = 0.013) or ER-negative (p = 0.0002) tumors. Patients with PR-positive tumors also had higher MALAT1 expression than those with PR-negative tumors (p < 0.0001). In patients with positive hormone receptors or low tumor grade, tumors with high MALAT1 expression were more likely to recur. Survival analysis showed that patients with high expression of MALAT1 had a twofold increase in risk of relapse (p = 0.0083) compared to those with low expression. This association remained significant after adjustment for age at surgery, disease stage, tumor grade, and hormone receptor status. Meta-analysis showed that high MALAT1 expression was associated with poor relapse-free survival in patients with hormone receptor-positive tumors (HR 1.44, 95% CI 1.08-1.92).

Conclusions: High expression of lncRNA MALAT1 is associated with breast cancer relapse and may play a role in tumor progression.

Keywords: Breast cancer; Estrogen receptor; MALAT1; Meta-analysis; Survival.

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Conflict of interest statement

Disclosure of potential conflicts of interest

None

Figures

Figure 1
Figure 1. Associations of MALAT1 expression with patient survival.
A) Kaplan-Meier estimates for relapse-free survival by high, mid, and low MALAT1 expression. B) Kaplan-Meier estimates for overall survival by high, mid, and low MALAT1 expression. C) Kaplan-Meier estimates for relapse-free survival by high, mid, and low MALAT1 expression in hormone receptor positive patients. D) Kaplan-Meier estimates for overall survival by high, mid, and low MALAT1 expression in hormone receptor positive patients.
Figure 2
Figure 2. Meta-analysis of the association between MALAT1 expression and breast cancer survival.
A) Meta-analysis of the association between MALAT1 expression and relapse-free survival. B) Meta-analysis of the association between MALAT1 expression and overall survival.
Figure 3
Figure 3. Meta-analysis of the association between MALAT1 expression and breast cancer survival in ER-positive patients.
A) Meta-analysis of the association between MALAT1 expression and relapse-free survival in ER-positive patients. B) Meta-analysis of the association between MALAT1 expression and overall survival in ER-positive patients.
Figure 4
Figure 4. Methylation status and MALAT1 expression.
A) A screenshot from the UCSC Genome Browser shows the CpG island in the MALAT1 promoter and probes included in the Illumina HumanMethylation450 BeadChip for measuring methylation in the CpG sites. B) Scatter plot shows the correlation between MALAT1 expression and promoter methylation in breast cancer using the TCGA data.
See this image and copyright information in PMC

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