Lan Xi, Zhang Heng, Chen Ze-Yan, Wang Jing, Zhang Shi-Chang, Li Qing, Ke Juan-Yu, Wei Wei, Huang Rong, Tang Xi, Chen Si-Ping, Huang Ting-Ting, Zhou Yi-Wen
Clinical Laboratory Center, Shenzhen Hospital, Southern Medical University, Shenzhen 518101, Guangdong Province, China.
World J Gastroenterol. 2025 Apr 7;31(13):100566. doi: 10.3748/wjg.v31.i13.100566.
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.
To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.
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. , co-culture experiments, migration assays, apoptosis detection, and enzyme-linked immunosorbent assay were conducted. , 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.
SOCS2 overexpression inhibited Treg cell activity, reducing LIHC cell migration and invasion while increasing apoptosis. , SOCS2 suppressed tumor growth and metastasis, confirming its therapeutic potential.
SOCS2 modulates CD4 T function in the TME, contributing to LIHC progression. Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.
肝细胞肝癌（LIHC）是一种侵袭性很强的癌症，由于其复杂的肿瘤微环境（TME）和免疫逃逸，预后较差。调节性T细胞（Tregs）在肿瘤进展中起关键作用。细胞因子信号转导抑制因子2（SOCS2）作为一种关键的免疫调节因子，可能调节Treg活性并影响LIHC的生长和转移。
探讨SOCS2如何影响LIHC中Treg的活性及其对肿瘤生长和转移的影响。
使用基因集富集分析、利用表达数据估计恶性肿瘤中的基质和免疫细胞以及通过估计RNA转录本的相对亚群进行细胞类型鉴定，对来自癌症基因组图谱数据库的LIHC转录组数据进行分析，以评估免疫途径和Treg浸润情况。使用加权基因共表达网络分析和机器学习确定关键的预后基因。进行了共培养实验、迁移试验、凋亡检测和酶联免疫吸附测定。使用苏木精和伊红染色、末端脱氧核苷酸转移酶dUTP缺口末端标记和免疫组织化学分析的皮下和肺转移小鼠模型评估肿瘤生长、转移和凋亡情况。
SOCS2过表达抑制Treg细胞活性，减少LIHC细胞的迁移和侵袭，同时增加凋亡。此外，SOCS2抑制肿瘤生长和转移，证实了其治疗潜力。
SOCS2调节TME中CD4 T细胞的功能，促进LIHC进展。靶向SOCS2为治疗LIHC提供了一种潜在的治疗策略。
