The role of SPP1 in evaluating the prognosis, immune infiltration, and drug sensitivity of hepatocellular carcinoma

by Kai Cui, Xia Li, Yongrun Li, Zhong Li, Du Wang, Xinhong Wang, Shuxin Qin, Junjie Li, Jiaye Long Background Secretory phosphoprotein 1 (SPP1) has been linked to tumor progression and immune regulation, but its prognostic value, impact on the tumor immune microenvironment (TIME), and drug sensitivity in HCC remain unclear. Methods We performed a pan-cancer analysis using TIMER and validated SPP1 upregulation in six GEO datasets (GSE45436, GSE54236, GSE121248, GSE76427, GSE64041, and GSE60502) and HPA protein data.

In TCGA-LIHC, we assessed overall survival (OS) and progression-free survival (PFS) using univariate/multivariate Cox analyses, ROC analysis, and a calibrated nomogram. We identified differentially expressed genes (DEGs) and performed GO/KEGG and GSEA analyses.

Immune infiltration was estimated with CIBERSORT and TIMER, and relationships with immune checkpoints were explored. Drug sensitivity was predicted with pRRophetic using GDSC data.

In vitro , SPP1 was knocked down or overexpressed in HCC cell lines to evaluate effects on proliferation, migration, invasion, and apoptosis via qRT-PCR, Western blot, CCK-8, colony formation, wound healing, Transwell invasion, and TUNEL assays.