Furthermore, single-cell RNA-seq analysis demonstrated that SPP1 controlled the interaction between HCC cells and macrophages through SPP1/CD44 and SPP1-PTGER4 signaling, and in vitro data also showed that SPP1 induced the polarization of macrophages to M2-like tumor-associated macrophages (TAMs) (52) (Figure 1B). This evidence concerns the gene SPP1 and neoplasm.