Combined the SMAC mimetic and BCL2 inhibitor sensitizes neoadjuvant chemotherapy by targeting necrosome complexes in tyrosine aminoacyl-tRNA synthase-positive breast cancer

摘要

Aminoacyl-tRNA synthetases (ARSs) are vital proteins in breast cancer patients responsive to chemotherapy. a Overview of the study design. b Unsupervised hierarchical clustering analysis of proteins identified in the nCR and CR groups (top-ranked proteins were indicated as gene names). c Gene Ontology terms for biological process obtained using the ToppGene Suite gene list enrichment analysis. Red (#1 to #26) and blue (#27 to #52) indicate biological processes enriched in the nCR and CR group, respectively. d Differentially expressed proteins are depicted on volcano plots (the red dotted line indicates upregulation in nCR, and the blue dotted line indicates upregulation in CR: P < 0.05; the gray dotted line indicates FDR < 5%). e Pathway enrichment analysis of 20 top-ranked proteins showing statistical significance based on intensity ratio (P < 0.05, left: red dot, upregulation in nCR, and blue dot, upregulation in CR) and molecular function categories of each protein based on Gene Ontology biological process (right). f Overview of the protein interaction network model. Colors of nodes indicate the expression levels of quantified proteins. The thickness of the gray line indicates the protein-protein interaction score provided in the STRING public database (red circle, upregulation in nCR; blue circle, upregulation in CR). CR, complete remission; nCR, non-complete remission