SPP1 and colorectal carcinoma: In addition, secreted Phosphoprotein 1(SPP1) is a secreted cytokine closely associated with tumorigenesis, invasion, and metastasis (101, 102).Single-cell transcriptomic analyses also revealed the presence of a high-expressing SPP1+ macrophage subpopulation in high-grade CRC, characterized by robust SASP features and serving as a critical component of the TME that contributes to tumor senescence (103).