Gu Mei-Ying, Ma Wan-Long, Ma Zi-Min, Ma Li-Na, Ding Xiang-Chun
Medical Univercity, Ningxia, 750004, China.
Department of Infectious Diseases, General Hospital of Ningxia Medical University, 804 Shengli Street, Xingqing District, Yinchuan, 750004, Ningxia, China.
Sci Rep. 2025 Mar 24;15(1):10111. doi: 10.1038/s41598-025-94504-1.
Hepatocellular carcinoma (HCC) is a prevalent and fatal tumor globally, characterized by a complex pathogenesis and poor prognosis. Despite significant advancements in the application of immune checkpoint inhibitors (ICIs) for cancer treatment, the efficacy of immunotherapy in HCC remains suboptimal. PSMD2, a crucial regulator of the ubiquitin-proteasome system, has attracted increasing attention for its involvement in various cancers; however, its functions and mechanisms in HCC are still poorly understood. This study aims to investigate the expression of PSMD2 in HCC, its association with prognosis, and its interaction with immune checkpoints, thus establishing a foundation for further exploration of its role in immune evasion in HCC. We analyzed the expression levels of PSMD2 in HCC and adjacent normal tissues utilizing the GEPIA and TIMER databases. Cox regression analysis was performed using R software to evaluate the relationship between PSMD2 expression and prognosis. Furthermore, we assessed the correlation between PSMD2 and immune cell infiltration, as well as immune checkpoints, including PD1, PD-L1, and CTLA-4, using R tools. Additionally, we examined the association between PSMD2 expression and immune therapy response through Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Finally, we constructed a protein-protein interaction (PPI) network using the STRING database and Cytoscape software, followed by Gene Set Enrichment Analysis (GSEA). PSMD2 was significantly overexpressed in HCC and was closely correlated with poor prognosis (HR = 1.61, P = 2.0e-4). Immune infiltration analysis demonstrated that PSMD2 was positively correlated with several immune checkpoint genes, including PD1, PD-L1, and CTLA-4, as well as various immune cell types. TIDE analysis indicated that elevated PSMD2 expression was significantly associated with increased immune evasion potential and a poor response to immunotherapy. Furthermore, GSEA enrichment analysis revealed that PSMD2 is primarily enriched in the p53 signaling pathway, the ubiquitin-mediated proteolysis pathway, and other cancer-related pathways. The elevated expression of PSMD2 in HCC is not only correlated with poor prognosis but may also play a role in immune evasion by modulating tumor immunity, thereby affecting patient responses to immunotherapy. Consequently, PSMD2 presents a promising novel therapeutic target and potential biomarker for immunotherapy in HCC.
肝细胞癌（HCC）是全球范围内一种常见且致命的肿瘤，其发病机制复杂，预后较差。尽管免疫检查点抑制剂（ICIs）在癌症治疗中的应用取得了显著进展，但免疫疗法在HCC中的疗效仍不尽人意。PSMD2是泛素 - 蛋白酶体系统的关键调节因子，因其在多种癌症中的作用而受到越来越多的关注；然而，其在HCC中的功能和机制仍知之甚少。本研究旨在探讨PSMD2在HCC中的表达、其与预后的关系以及与免疫检查点的相互作用，从而为进一步探索其在HCC免疫逃逸中的作用奠定基础。我们利用GEPIA和TIMER数据库分析了PSMD2在HCC及相邻正常组织中的表达水平。使用R软件进行Cox回归分析，以评估PSMD2表达与预后之间的关系。此外，我们使用R工具评估了PSMD2与免疫细胞浸润以及免疫检查点（包括PD1、PD - L1和CTLA - 4）之间的相关性。另外，我们通过肿瘤免疫功能障碍和排除（TIDE）分析研究了PSMD2表达与免疫治疗反应之间的关联。最后，我们使用STRING数据库和Cytoscape软件构建了蛋白质 - 蛋白质相互作用（PPI）网络，随后进行基因集富集分析（GSEA）。PSMD2在HCC中显著过表达，且与不良预后密切相关（HR = 1.61，P = 2.0e - 4）。免疫浸润分析表明，PSMD2与包括PD1、PD - L1和CTLA - 4在内的多个免疫检查点基因以及多种免疫细胞类型呈正相关。TIDE分析表明，PSMD2表达升高与免疫逃逸潜力增加和免疫治疗反应不佳显著相关。此外，GSEA富集分析显示，PSMD2主要富集于p53信号通路、泛素介导的蛋白水解途径和其他癌症相关途径。PSMD2在HCC中的高表达不仅与不良预后相关，还可能通过调节肿瘤免疫在免疫逃逸中发挥作用，从而影响患者对免疫治疗的反应。因此，PSMD2是HCC免疫治疗中一个有前景的新型治疗靶点和潜在生物标志物。
