Decoding the Clinical and Therapeutic Significance of MEAK7 in Triple-Negative Breast Cancer Through Integrative...

Triple-negative breast cancer (TNBC) represents a clinically challenging breast cancer (BC) subtype, characterized by aggressive behavior, high recurrence risk, and limited therapeutic options. MEAK7 has been identified as an alternative mTORC1 signaling pathway regulator; however, its role in BC and TNBC remains uninvestigated. This study aims to assess MEAK7 expression, prognostic significance, and therapeutic potential. We employed public datasets, including TCGA, bc-GenExMiner v5.2, GEPIA3, DOSurvive platforms, Kaplan-Meier Plotter, UALCAN, TIMER2.0, STRING, ENCORI, HPA, miRDB, TargetScan, and CRISPRdb. MEAK7 expression was significantly elevated in BC tissues versus normal breast tissue. MEAK7 expression was pronounced in TNBC and basal-like subtypes, with hypomethylation of its promoter region in TNBC. Elevated MEAK7 expression correlated with reduced disease-free survival (DFS) in TNBC and basal-like. Multivariate Cox regression identified MEAK7 as a significant prognostic factor for overall survival, independent of age and tumor stage. MEAK7 showed CRISPR-targetable gRNA profiles with high on-target efficiency and minimal off-target effects. Analyses revealed negative correlation with tumor-suppressive RNAs (miR-149-3p, miR-135a-5p, and LINC00993) and positive correlation with aggressive regulators (miR-135b-5p and HIF1A-AS2). This study represents one of the initial comprehensive and multi-platform bioinformatic analyses demonstrating that MEAK7 exhibits elevated expression in breast cancer, particularly within the aggressive TNBC. The findings indicate that MEAK7 may serve as a promising prognostic biomarker in TNBC biology and suggest its viability as a molecular candidate for future investigation in targeted therapeutic strategies.