前列腺癌(PCa)是一种免疫冷肿瘤,对这种行为的分子过程知之甚少。在这项研究中,我们使用旨在研究癌症进展和免疫反应的两个NanoString分析小组调查了中危PCa的主要队列(n=51).我们确定了与生化复发(BCR)和临床风险相关的差异表达基因(DEGs)和通路。使用TCGA-PRAD队列进行验证性分析。值得注意的DEG包括胶原蛋白,如COL1A1,COL1A2和COL3A1。胶原蛋白分布的变化可能会影响肿瘤微环境(TME)中的免疫活性。此外,免疫相关的DEGs,如THY1,IRF5和HLA-DRA也被鉴定。富集分析强调了与血管生成相关的途径,TGF-β,UV响应,EMT。在39个显著的DEG中,使用协调组数据库将11个(28%)鉴定为ZEB1的EMT靶基因。ZEB1表达升高与BCR风险降低相关。免疫景观分析显示,ZEB1与TME中免疫抑制细胞类型增加有关,如幼稚B细胞和M2巨噬细胞。ZEB1和SNAI1的表达增加与免疫检查点表达升高相关。在未来,EMT的调节可能有利于克服冷肿瘤中的免疫疗法抗性,比如PCa。
Prostate cancer (PCa) is an immunologically cold tumor and the molecular processes that underlie this behavior are poorly understood. In this study, we investigated a primary cohort of intermediate-risk PCa (n = 51) using two NanoString profiling panels designed to study cancer progression and immune response. We identified differentially expressed genes (DEGs) and pathways associated with biochemical recurrence (BCR) and clinical risk. Confirmatory analysis was performed using the TCGA-PRAD cohort. Noteworthy DEGs included
collagens such as COL1A1, COL1A2, and COL3A1. Changes in the distribution of
collagens may influence the immune activity in the tumor microenvironment (TME). In addition, immune-related DEGs such as THY1, IRF5, and HLA-DRA were also identified. Enrichment analysis highlighted pathways such as those associated with angiogenesis, TGF-beta, UV response, and EMT. Among the 39 significant DEGs, 11 (28%) were identified as EMT target genes for ZEB1 using the Harmonizome database. Elevated ZEB1 expression correlated with reduced BCR risk. Immune landscape analysis revealed that ZEB1 was associated with increased immunosuppressive cell types in the TME, such as naïve B cells and M2 macrophages. Increased expression of both ZEB1 and SNAI1 was associated with elevated immune checkpoint expression. In the future, modulation of EMT could be beneficial for overcoming immunotherapy resistance in a cold tumor, such as PCa.