Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification

Abstract

It is unclear whether the methyltransferase-like 14 (METTL14) protein promotes or suppresses cancer growth. We examined the association between METTL14 expression, cancer progression, and patient prognosis in a total of 398 breast cancer tissue specimens. Significantly fewer cancer tissue specimens compared with normal breast tissue expressed high levels of METTL14 (52.8% vs. 75.0%). METTL14 expression was negatively associated with tumor grade and positively associated with patient age, estrogen, and progesterone receptor status. High METTL14 expression was more common in luminal A and luminal B tissue (75.9% and 60.8%, respectively), compared with human epidermal growth factor receptor 2- (HER2-) enriched and triple-negative breast cancer (TNBC) samples (38.2% and 18.6%, respectively). In multiple logistic regression analysis, independent predictors of METTL14 expression in breast cancer included higher tumor grade ( $\text{odds}\text{ratio}\left(\text{OR}\right)=0.494$ , 95% confidence interval (CI): 0.289–0.844; $P=0.010$ ), TNBC subtype ( $\text{OR}=0.109$ , 95% CI: 0.054–0.222; $P<0.001$ ), and HER2-enriched subtype ( $\text{OR}=0.298$ , 95% CI: 0.156–0.567; $P<0.001$ ). No clear relationship was observed between patient prognosis and METTL14 expression. It appears that downregulated METTL14 expression in breast cancer is associated with tumor grade and molecular classification.