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 asCOL1A1,COL1A2, andCOL3A1. Changes in the distribution of collagens may influence the immune activity in the tumor microenvironment (TME). In addition, immune-related DEGs such asTHY1,IRF5, andHLA-DRAwere 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 forZEB1using the Harmonizome database. ElevatedZEB1expression correlated with reduced BCR risk. Immune landscape analysis revealed thatZEB1was associated with increased immunosuppressive cell types in the TME, such as naïve B cells and M2 macrophages. Increased expression of bothZEB1andSNAI1was 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.
前列腺癌（PCa）是一种免疫学上的“冷肿瘤”，其背后的分子机制尚不明确。本研究采用两个NanoString分析面板，对一个中等风险前列腺癌原发队列（n=51）进行了分析，旨在探究癌症进展与免疫反应的相关机制。我们识别了与生化复发（BCR）及临床风险相关的差异表达基因（DEGs）和信号通路，并利用TCGA-PRAD队列进行了验证分析。值得注意的差异表达基因包括胶原蛋白基因如COL1A1、COL1A2和COL3A1。胶原蛋白分布的变化可能影响肿瘤微环境（TME）中的免疫活性。此外，研究还发现了THY1、IRF5和HLA-DRA等免疫相关差异表达基因。富集分析突出了与血管生成、TGF-β信号、紫外线反应及上皮间质转化（EMT）相关的通路。在39个显著差异表达基因中，通过Harmonizome数据库鉴定出11个（28%）为ZEB1的EMT靶基因。ZEB1表达升高与生化复发风险降低相关。免疫景观分析显示，ZEB1与肿瘤微环境中免疫抑制性细胞类型（如初始B细胞和M2型巨噬细胞）的增加有关。ZEB1和SNAI1的共同高表达与免疫检查点表达升高相关。未来，调控上皮间质转化可能有助于克服如前列腺癌这类冷肿瘤的免疫治疗耐药性。
肿瘤(癌症)患者之家