Fig. 6: Proposed model of action for PRSS22-mediated inflammation-associated colorectal cancer progression.

Within the context of chronic inflammation, PRSS22 expression is progressively upregulated in colorectal epithelial cells. Elevated PRSS22 suppresses ferroptosis by inhibiting HMOX1-mediated iron release and ROS accumulation, thereby supporting tumor cell survival. Concurrently, PRSS22 proteolytically cleaves OPN into active fragments that enhance the migratory and metastatic potential of CRC cells. In the tumor microenvironment, PRSS22 promotes the polarization of macrophages toward an immunosuppressive M2-like phenotype, particularly increasing the proportion of SPP1⁺ macrophages, which further contributes to immune evasion and poor prognosis. The schematic illustration was created using Adobe Illustrator (version 27.5).