{"title":"PSMD2基因在肝细胞癌中的表达及其与免疫检查点和预后的关系","authors":"Mei-Ying Gu, Wan-Long Ma, Zi-Min Ma, Li-Na Ma, Xiang-Chun Ding","doi":"10.1038/s41598-025-94504-1","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"10111"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933310/pdf/","citationCount":"0","resultStr":"{\"title\":\"Expression of PSMD2 gene in hepatocellular carcinoma and its correlation with immune checkpoints and prognosis.\",\"authors\":\"Mei-Ying Gu, Wan-Long Ma, Zi-Min Ma, Li-Na Ma, Xiang-Chun Ding\",\"doi\":\"10.1038/s41598-025-94504-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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引用次数: 0
摘要
肝细胞癌(HCC)是一种全球常见的致死性肿瘤,其发病机制复杂,预后差。尽管免疫检查点抑制剂(ICIs)在癌症治疗中的应用取得了重大进展,但免疫治疗在HCC中的疗效仍然不理想。PSMD2是泛素-蛋白酶体系统的关键调节因子,因其参与多种癌症而引起越来越多的关注;然而,其在HCC中的功能和机制仍然知之甚少。本研究旨在探讨PSMD2在HCC中的表达、与预后的关系以及与免疫检查点的相互作用,为进一步探讨其在HCC免疫逃避中的作用奠定基础。我们利用GEPIA和TIMER数据库分析了PSMD2在HCC和邻近正常组织中的表达水平。采用R软件进行Cox回归分析,评价PSMD2表达与预后的关系。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。此外,我们通过肿瘤免疫功能障碍和排斥(TIDE)分析检测了PSMD2表达与免疫治疗反应之间的关系。最后,我们利用STRING数据库和Cytoscape软件构建了蛋白-蛋白相互作用(PPI)网络,并进行了基因集富集分析(GSEA)。PSMD2在HCC中显著过表达,与预后不良密切相关(HR = 1.61, P = 2.0e-4)。免疫浸润分析表明,PSMD2与多种免疫检查点基因PD1、PD-L1、CTLA-4以及多种免疫细胞类型呈正相关。TIDE分析显示PSMD2表达升高与免疫逃避潜能增加和免疫治疗反应差显著相关。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通路和其他癌症相关通路。PSMD2在HCC中的表达升高不仅与预后不良相关,还可能通过调节肿瘤免疫参与免疫逃避,从而影响患者对免疫治疗的应答。因此,PSMD2是一种很有前景的肝癌免疫治疗新靶点和潜在的生物标志物。
Expression of PSMD2 gene in hepatocellular carcinoma and its correlation with immune checkpoints and prognosis.
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.
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