Specifically, OPN derived from tumor stroma has been identified to mediate numerous signaling pathways that lead to tumor progression, such as cancer-associated fibroblast transformation in breast cancer (39), promotion of a stem-like phenotype in hepatocellular carcinoma (40), and activation of the PI3K (41) and NF-κB pathways (42, 43). Here, SPP1 is linked to neoplasm.