Moreover, pathway analysis revealed that SPP1+APOE+ TAM were regulated by the HIF-1 signaling pathway (Supplementary Fig. 3C, 3D), inducing expression of VEGFA, LDHA, and ALDOA46,47, which not only promotes hypoxia (Fig. 4g) but is another approach to induce EMT in tumor cells48. The gene discussed is VEGFA; the disease is neoplasm.