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. Metastasisspecific genes were identified. SPP1-associated functions were explored using GO enrichment, KEGG pathway analysis, and GSVA. Prognostic value was assessed. SPP1 expression was evaluated in 30 CRC specimens (15 HIV-positive, 15 HIV-negative) via immunohistochemistry.

SPP1 exhibited a metastasis-specific expression pattern. High SPP1 correlated with significantly 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 organization, cell adhesion, immune response, inflammation, and receptor binding. KEGG analysis showed enrichment in HIV-1 infection pathways. However, overall SPP1 expression did not significantly differ between HIV-positive and HIV-negative CRC tissues. Diffuse SPP1 protein expression was noted in an HIV-positive signet-ring cell carcinoma.

SPP1 is a pivotal driver of CRC metastasis and immune regulation in the tumor microenvironment, 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 independently predicts poor survival. Its prognostic value is confirmed, warranting investigation into its role in specific HIV-related carcinomas.