Sterol carrier protein 2 (SCP2) plays a critical role in intracellular lipid transport and metabolism across human tissues. The objective of this study was to perform a comprehensive pan-cancer analysis of SCP2, evaluating its expression, prognostic significance, and functional mechanisms.

We analyzed SCP2 expression using data from TCGA and GTEx databases. Prognostic significance was evaluated via Kaplan-Meier and Cox regression analyses, alongside nomogram construction. Functional mechanisms were investigated through GO, KEGG, and GSEA enrichment analyses. Genetic alterations, DNA methylation, single-cell functions, and immune infiltration were assessed using multiple bioinformatic platforms. The effects of SCP2 on cancer cell proliferation, migration, apoptosis, and sensitivity to ferroptosis were verified by in vitro experiments.

SCP2 was differentially expressed in multiple tumors and correlated with clinical outcomes and immune infiltration. Enrichment analyses linked SCP2 to lipid metabolism-related pathways. In colon adenocarcinoma (COAD), SCP2 was downregulated and functioned as a tumor suppressor, as its overexpression inhibited proliferation and migration, promoted apoptosis, and strongly enhanced ferroptosis sensitivity in colon cancer cells.

Our pan-cancer analysis highlights the broad biological and clinical significance of SCP2. It functions as a tumor suppressor and key regulator of ferroptosis in COAD, highlighting its potential as a promising therapeutic target.