Suppressor of cytokine signaling 2 modulates regulatory T cell activity to suppress liver hepatocellular carcinoma growth and metastasis.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment (TME) and immune evasion. Regulatory T cells (Tregs) play a critical role in tumor progression. Suppressor of cytokine signaling 2 (SOCS2), a key immune regulator, may modulate Treg activity and impact LIHC growth and metastasis. AIM: To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis. METHODS: LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis, Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data, and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration. Key prognostic genes were identified using Weighted Gene Co-expression Network Analysis and machine learning. In vitro, co-culture experiments, migration assays, apoptosis detection, and enzyme-linked immunosorbent assay were conducted. In vivo, tumor growth, metastasis, and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining, Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling, and immunohistochemistry analyses. RESULTS: SOCS2 overexpression inhibited Treg cell activity, reducing LIHC cell migration and invasion while increasing apoptosis. In vivo, SOCS2 suppressed tumor growth and metastasis, confirming its therapeutic potential. CONCLUSION: SOCS2 modulates CD4(+) T function in the TME, contributing to LIHC progression. Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.