PSMB2通过细胞外基质-受体相互作用通路影响胰腺导管腺癌预后的多维度分析

Multidimensional analysis of the prognostic impact of PSMB2 in pancreatic ductal adenocarcinoma via the ECM-receptor interaction pathway

摘要:

背景与目的 蛋白酶体20S亚基β2（PSMB2）在多种肿瘤中异常表达并参与肿瘤进展，但其在胰腺导管腺癌（PDAC）中的表达特征、预后价值及潜在机制尚不明确。本研究旨在基于生物信息学分析及临床样本验证，探讨PSMB2在PDAC中的临床意义及其可能作用机制。方法 整合TCGA及GEO数据库（GSE62452、GSE15471）中PDAC表达谱及临床数据，分析PSMB2表达差异及其与预后的关系。采用Kaplan-Meier生存分析及Cox回归评估其预后价值。收集76例PDAC组织进行免疫组织化学验证，并分析其与临床病理特征的关联。利用GSEA及相关性分析探讨潜在分子机制，通过ssGSEA分析免疫细胞浸润情况，并结合TCIA数据库预测免疫治疗反应，基于GDSC数据库评估药物敏感性。结果 PSMB2在PDAC组织中呈明显高表达，且高表达患者总体生存期明显缩短（均P<0.05）。多因素Cox分析显示PSMB2是PDAC预后的独立危险因素。免疫组化结果与数据库分析一致。PSMB2表达与淋巴结转移、病理分期及分化程度相关。GSEA分析提示其可能参与细胞外基质（ECM）-受体相互作用通路。相关性分析显示PSMB2与多种ECM相关基因呈正相关。免疫分析显示PSMB2与多种免疫细胞浸润相关，并可能影响免疫治疗反应。此外，PSMB2高表达与多种靶向药物敏感性增加相关。结论 PSMB2在PDAC中高表达并与不良预后密切相关，是独立预后指标，其作用机制可能与ECM-受体相互作用通路及肿瘤免疫微环境调控相关，有望成为潜在治疗靶点。

Abstract:

Background and Aims Proteasome 20S subunit β2 (PSMB2) has been implicated in tumor progression in multiple cancers; however, its expression pattern, prognostic value, and underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aimed to investigate the clinical significance and potential mechanisms of PSMB2 in PDAC through integrated bioinformatics analysis and clinical validation.Methods Expression profiles and clinical data from TCGA and GEO datasets (GSE62452 and GSE15471) were analyzed to evaluate PSMB2 expression and its prognostic significance. Kaplan-Meier survival analysis and Cox regression models were used. Immunohistochemistry was performed on 76 PDAC samples for validation. Gene Set Enrichment Analysis (GSEA) and correlation analyses were conducted to explore potential mechanisms. Immune cell infiltration was assessed using ssGSEA, and immunotherapy response was predicted using TCIA data. Drug sensitivity was analyzed based on the GDSC database.Results IPSMB2 expression was significantly upregulated in PDAC tissues, and high expression was associated with poorer overall survival (all P<0.05). Multivariate Cox analysis identified PSMB2 as an independent prognostic factor. Immunohistochemical results were consistent with bioinformatics findings. PSMB2 expression correlated with lymph node metastasis, pathological stage, and differentiation. GSEA indicated enrichment in the ECM-receptor interaction pathway. Correlation analysis showed positive associations with multiple ECM-related genes. Additionally, PSMB2 was associated with immune cell infiltration and predicted immunotherapy response. Higher PSMB2 expression was also linked to increased sensitivity to several targeted agents.Conclusion PSMB2 is overexpressed in PDAC and is associated with poor prognosis, serving as an independent prognostic biomarker. Its role may involve regulation of the ECM-receptor interaction pathway and tumor immune microenvironment, highlighting its potential as a therapeutic target.