Abstract
BACKGROUND: Secreted frizzled-related protein (SFRP) is a crucial regulator of Wnt signaling, involved in multiple biological processes including cell proliferation and metastasis. Despite the accumulation of evidence that indicated that SFRPs are differentially expressed and play a key role in various malignancies, the function of different SFRPs in colorectal cancer (CRC) remains insufficiently studied. METHODS: Multicenter databases, including GEPIA, cBioPortal, UALCAN, Pathway Commons, STRING, TIMER, CCLE, and LinkedOmics, comprehensively analyzed differential expression, prognostic value, genetic alterations, signaling pathways, immune cell infiltration, and associated genes of the SFRP family in CRC patients. Colony formation, wound healing, and transwell assays were performed to further validate in vitro. RESULTS: SFRP family members were differentially expressed in CRC, with each member showing varying degrees of genetic alterations. Except for SFRP5, the remaining members show a significant correlation with immune cells. Interestingly, only SFRP2 significantly correlated with CRC prognosis and stage. Additionally, SFRP2 participated in a number of critical biological processes, including metastasis and cell proliferation. Moreover, cell function assays suggested the elimination of SFRP2 inhibits the proliferation, migration, and invasion of HCT116 cells. CONCLUSIONS: The differential expression of SFRP2 is closely associated with the prognosis of CRC patients. In addition, abnormal expression of SFRP2 has a significant impact on the progression of CRC, including proliferation, migration, and invasion. SFRP2 may become a novel prognostic factor for CRC.