Abstract
Abstract Background: Malic enzyme 1 (ME1) catalyzes malate to pyruvate and thus promotes glycolysis, playing a part in the Warburg effect. Recently, several researches have revealed its crucial role in cancer metastasis. KM-plotter, an online analysis tool, showed high ME1 mRNA level was related to poorer RFS and OS. Herein, we explore the prognostic effect of ME1 on invasive breast cancer in Chinese patients and its effect on metastasis in vitro. Methods: 220 patients with early breast cancer were included in this study. ME1 expression was evaluated semi-quantitatively with tissue microarray-based immunohistochemistry. The relationships between ME1 expression level and clinicopathological features were explored. Survival analyses were carried out by Kaplan-Meier test and COX proportional hazard model. MCF-7 and MDA-MB-468 cell lines were then used for in vitro cell migration and invasion assays. Results: High expression of ME1 was observed in 51.5% patients. The median follow-up period was 28.9 months (range 0.5-34.0). In correlation analyses, compared with ME1-low cases, ME1-high cases were significantly associated with larger tumor size (P=0.036), positive lymph nodes (P<0.001) and positive lymph-vascular invasion (P=0.003), and tended to be HER2 positive (P=0.094). Survival analysis by Kaplan-Meier test showed high ME1 expression was significantly correlated with poorer recurrence free survival (RFS) (P=0.015). Multivariate analysis identified high ME1 expression as an independent prognostic factor for RFS (P=0.035, HR=5.072 [1.121, 22.942]). Stratified analysis revealed high ME1 expression was related to poorer RFS among cases more than 45 years old (P=0.029, HR=9.833 [1.269, 76.164]) and among those with Ki67 index ≥20% (P=0.038, HR=3.805 [1.074, 13.486]). In vitro, HER2 positive cell line (SKBR3) and TNBC cell lines (MDA-MB-231, MDA-MB-468) showed high expression of ME1, while luminal cell line (MCF-7) showed low expression of ME1. Upregulation of ME1 in MCF-7 cell line remarkably enhanced its ability in migration and invasion, while knockdown of ME1 in MDA-MB-468 cell line had a profound inhibitory effect on migration and invasion. Conclusions: ME1 enhances migration and invasion of breast cancer cell lines and may be involved in early development of breast cancer metastasis. Thus, ME1 is a promising prognostic indicator and a potential therapeutic target. Citation Format: Liu C, Tao Z, Hu X. Malic enzyme 1 is a potential metastasis-related biomarker of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-45.
Published Version
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