Abstract / Summary
Abstract Purpose To investigate the expression characteristics of STOML2 in hepatocellular carcinoma (HCC) at mRNA, protein and subcellular localization levels, clarify its correlation with immune microenvironment, single-cell expression profile, drug resistance and prognosis, and verify its biological functions and mechanism in regulating HCC cell proliferation, invasion, migration and apoptosis via the PI3K/AKT signaling pathway. Method Bioinformatic analyses were performed using TCGA, CPTAC, HPA, TIMER2.0, TISCH and GEPIA2 databases to explore STOML2 expression, prognosis, immune infiltration, single-cell distribution and related signaling pathways. HCCLM3 cells with high STOML2 expression were selected to construct the siRNA-mediated knockdown model. CCK-8, Transwell, scratch assay, flow cytometry and Western blot were used to detect cell phenotypes and pathway protein changes. Result STOML2 was significantly upregulated in HCC tissues at mRNA and protein levels, with strong positive staining in HCC and moderate expression in normal liver tissues by HPA analysis. Paired sample analysis confirmed significantly higher STOML2 expression in HCC than in adjacent non-cancerous tissues (P < 0.001). High STOML2 expression predicted shorter overall survival (HR = 1.67, P < 0.05) and showed moderate prognostic value for 1‑year survival (AUC = 0.690). STOML2 was mainly enriched in malignant HCC cells at single-cell level, and positively correlated with tumor-associated immune cell infiltration and PD-L1, CTLA-4, LAG3 expression. It was also positively correlated with HIF1A, SLC7A11 and AKT1, suggesting a role in sorafenib resistance. GSEA and correlation analysis verified close association between STOML2 and the PI3K/AKT pathway. In vitro experiments showed that STOML2 knockdown markedly inhibited proliferation, invasion and migration, promoted apoptosis, and reduced p‑PI3K and p‑AKT levels without altering total PI3K and AKT. Conclusion STOML2 is highly expressed in HCC and correlated with poor prognosis, immune suppression microenvironment and potential drug resistance. STOML2 promotes HCC progression by activating the PI3K/AKT signaling pathway, and may serve as a promising prognostic biomarker and therapeutic target for HCC.