SPP1 and cancer: Finally, we also explored the signaling pathways that five signature genes involved, and the results showed that SPP1 is an extracellular matrix (ECM) component, which has been proven to be associated with various cancer proliferation and differentiation processes [12, 13], while ECM components and factors can affect the cell cycle by activating the PI3K-AKT signaling pathway through the integrins IGTA and IGTB, which are closely related to the proliferation and apoptosis processes of cancer cells (Fig. 9).