Interestingly, despite the strong correlation of the liver metastasis signature with CMS4, the expression of stromal genes (FAP, smooth muscle actin (ACTA2)) and the ESTIMATE tumor stroma signature were not significantly different between liver metastases and paired primary tumors (Figure 6E–G), while such genes are significantly more expressed in CMS4 tumors compared to CMS1-3 tumors [19,20]. The gene discussed is ACTA2; the disease is neoplasm.