KRT14 as a potential prognostic marker for metastasis in metaplastic breast carcinoma

Abstract

Metaplastic breast cancer (MBC) is an aggressive breast cancer subtype with poor prognosis. To elucidate underlying genomic aberrations driving MBC, we conducted integrated transcriptomic analyses of MBC tumors and basal breast cancer cell lines with various transitioning phases (xE = epithelial phase clone, xM = mesenchymal phase clone and xEM = Epithelial-mesenchymal clone). Differential gene expression analysis between MBC vs non-MBC samples as well as between epithelial-mesenchymal (xEM) transitioning cells vs parental cells revealed 12 commonly dysregulated genes intersected from both the datasets meditates pathways governing EMT, migration, proliferation and metastasis. Further investigation onto those genes based on multi-omics approaches that include survival analysis, correlated expression patterns and interactomics indicated KRT14 had a key role in promoting MBC aggression through Epithelial mesenchymal transition leading to metastasis. Moreover, NPR3 was found to be a possible link between KRT14 and EMT in metastasis. To our knowledge, this is the first evident gene expression study to investigate the potential association between the expression of KRT14 and NPR3 and metastasis in MBC, and their potential involvement in the epithelial-mesenchymal transition (EMT) process. These mechanistic and prognostic insights gained can lead to targeted therapeutics against this rare, refractory disease. Overall, this work highlights the effectiveness of integrated multi-omics in revealing gene expression pattern and predictive biomarkers for metaplastic breast cancer subtypes with poor prognosis.