Association of METTL14 expression with prognosis and immunotherapy in breast cancer

Background: Methyltransferase-like 14 (METTL14) is recognized as a key factor in the advancement and progression of breast cancer (BC). While its involvement in this context is acknowledged, many aspects of METTL14's functions remain unclear. We aimed to explore the function and potential mechanism of METTL14 in BC. Methods: The level of METTL14 in BC cell lines and tissues was evaluated using quantitative real-time polymerase chain reaction, immunohistochemistry, and western blotting methods. The cell counting kit-8 (CCK-8) assay, wound healing assay, and transwell chamber assay were employed to investigate the biological functions of METTL14 in BC. The relationship between immune characteristics and METTL14 was analyzed using the Tumor Immune Estimation Resource (TIMER) and Tumor-Immune System Interaction Database (TISIDB). The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapy response of BC patients. Multiplex immunofluorescence (mIF) was used to evaluate the expression of eight candidate markers of immune cell subsets and checkpoints in BC samples. Furthermore, a Kaplan-Meier survival analysis was performed to assess the prognostic significance of METTL14 in BC. Results: T cells, macrophages, and mast cells, while a negative correlation was observed with the abundance of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, and follicular helper T cells, as determined through immune analysis. METTL14 downregulation is associated with an immunosuppressive tumor microenvironment (TME), potentially through the upregulation of certain immunosuppressive factors. Results from mIF confirmed that low METTL14 expression correlates with high programmed death-1 (PD-1) expression. The analysis using the TIDE algorithm indicated that METTL14 expression was primarily negatively associated with the response to immunotherapy. Conclusions: METTL14 demonstrates significant predictive value regarding prognosis in BC. The METTL14 has the potential to serve as a predictive biomarker and a promising target for immunotherapy.