Molecular differences between CTC clusters and single CTCs. CTC clusters like single CTCs harbor the molecular hallmark of their primary tumor. By contrast, multiple pathways like cell–cell adhesion (desmosomes), stemness (surface markers and associated transcription factors), and proliferation (higher KI67) are up-regulated in CTC clusters. On the other hand, apoptosis and immune activation pathways like Major Histocompatibility Complex MHC type II presentation, T-cell activation, and Tumor Necrosis Factor TNF signaling are down-regulated. Epithelial to mesenchymal transition status of CTC clusters is crucial for single CTC migratory property but is debated for clusters. This figure was performed using free online Servier Medical Art at www.servier.com.