Introduction: Secreted phosphoprotein 1 (SPP1) is upregulated in cancers, but its role in metastatic colorectal cancer (CRC) and expression in HIV-associated CRC remain unclear. Methods: Transcriptomic data from the GEO and TCGA databases were analyzed. Metastasis-specific genes were identified. SPP1-associated functions were explored using GO enrichment, KEGG pathway analysis, and GSVA. Prognostic value was assessed. SPP1 expression was eval-uated in 30 CRC specimens (15 HIV-positive, 15 HIV-negative) via immunohistochemistry. Discussion: SPP1 is a pivotal driver of CRC metastasis and immune regulation in the tumor mi-croenvironment, and is associated with aggressive disease and poor outcomes. It shows strong potential as a prognostic biomarker. While HIV status did not broadly alter SPP1 expression, its specific pattern in certain HIV-associated carcinomas requires further study. Conclusion: SPP1 critically mediates metastasis and immune regulation in CRC and inde-pendently predicts poor survival. Its prognostic value is confirmed, warranting investigation into its role in specific HIV-related carcinomas.
Gao et al. (Tue,) studied this question.