Metastasis-Specific Biomarker SPP1 and its Characterization in Colorectal Cancer with HIV Infection

Secreted phosphoprotein 1 (SPP1) is upregulated in cancers, but its role in metastatic colorectal cancer (CRC) and expression in HIV-associated CRC remain unclear.

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.

SPP1 exhibited a metastasis-specific expression pattern. High SPP1 correlated with sig-nificantly elevated immune cell infiltration and adverse clinicopathological features: older age, mucinous adenocarcinoma, lymphatic invasion, advanced stage, high TN stage, MSI-H status, absence of polyps, and poor prognosis. GO enrichment linked SPP1 to extracellular matrix or-ganization, cell adhesion, immune response, inflammation, and receptor binding. KEGG analysis showed enrichment in HIV-1 infection pathways. However, overall SPP1 expression did not sig-nificantly differ between HIV-positive and HIV-negative CRC tissues. Diffuse SPP1 protein ex-pression was noted in an HIV-positive signet-ring cell carcinoma.

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.

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.