AUTHOR=Müller Christian , Oliveira-Ferrer Leticia , Müller Volkmar , Schmalfeldt Barbara , Windhorst Sabine 

TITLE=Transcriptome-based identification of key actin-binding proteins associated with high metastatic potential in breast cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1440276

DOI=10.3389/fmolb.2024.1440276

ISSN=2296-889X

ABSTRACT=<sec><title>Introduction</title><p>Actin-binding proteins (ABPs) are essential for the regulation of morphological plasticity required for tumor cells to metastasize. The aim of this study was to perform an unbiased bioinformatic approach to identify the key ABPs significantly associated with the metastatic potential of breast cancer cells.</p></sec><sec><title>Methods</title><p>Microarray data from 181 primary breast cancer samples from our hospital were used, and all genes belonging to the Gene Ontology term actin cytoskeleton organization were obtained from QuickGO. Association with metastasis-free survival probability was tested using Cox proportional hazards regression, and pairwise co-expression was tested by Pearson correlations. Differential expression between different subgroups was analyzed using Wilcoxon tests for dichotomous traits and Kruskal–Wallis tests for categorical traits. Validation was performed using four publicly available breast cancer datasets.</p></sec><sec><title>Results</title><p><italic>ARHGAP25</italic> was significantly associated with a low metastatic potential, and <italic>CFL1</italic>, <italic>TMSB15A</italic>, and <italic>ACTL8</italic> were significantly associated with a high metastatic potential. A significantly higher expression of <italic>CFL1</italic>, <italic>TMSB15A,</italic> and <italic>ACTL8</italic> mRNA was found in the more aggressive Her2-positive and triple-negative subtypes as well as in ER-negative samples. Also, these genes were co-expressed in the same tumors. However, only mRNA levels of <italic>CFL1</italic> were increased in pN1 compared to pN0 patients. External validation revealed that <italic>CFL1</italic> and <italic>TMSB15A</italic> had significant associations with consistent hazard ratios in two breast cancer cohorts, and among these, <italic>CFL1</italic> exhibited the highest hazard ratios.</p></sec><sec><title>Conclusion</title><p><italic>CFL1</italic> showed the strongest correlation with the metastatic potential of breast tumors. Thus, targeted inhibition of <italic>CFL1</italic> might be a promising approach to treat malignant breast cancer cells.</p></sec>