MAP3K1 Identified as a Prognostic Biomarker in Breast Cancer After Multi-omics Bioinformatics Analysis

Abstract

Abstract Background Despite significant advances in cancer research, cancer remains a major public health concern, with breast cancer being one of the leading causes of death among women. The mitogen-activated protein kinase kinase kinase 1 (MAP3K1) codes for a serine/threonine kinase abundant in the c-Jun N-terminal kinase, mitogen-activated protein kinase, and Nf-kappa-β pathways, which are involved in tumorigenesis. Methods Multi-omics bioinformatics analysis on the TCGA and METABRIC datasets from cBioPortal was conducted to analyze MAP3K1’s relevance in breast cancer. Other tools, including TIMER 2.0, Kaplan-Meier Plotter, UALCAN, and STRING, were implemented to provide additional insight into MAP3K1 in different types of omics data. Results Results revealed that, though MAP3K1 alterations are relatively uncommon overall, they are most common in breast cancer. These alterations mostly included truncating mutations and often co-occurred with alterations in PIK3CA, an already established biomarker in breast cancer research. Survival analysis indicated that MAP3K1 underexpression was strongly associated with lower patient survival. MAP3K1 was underexpressed for African Americans, triple-negative breast cancer patients, and stage 4 patients, while its phosphoprotein was overexpressed for these demographics. Conclusions Drug targets or other targeted therapy options that limit MAP3K1 phosphoprotein expression could potentially improve patient outcomes, especially for the aforementioned demographics. However, limited information is known about this phosphoprotein, so there is an unmet need to address this lack of knowledge and eventually find ways to combat its excessive expression in breast cancer.