Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Guangdong Second Provincial General Hospital, Guangzhou, P. R. China.
PLoS One. 2024 Aug 15;19(8):e0306525. doi: 10.1371/journal.pone.0306525. eCollection 2024.
Metastatic prostate cancer (mPCa) is a widespread disease with high mortality. Unraveling molecular mechanisms of disease progression is of utmost importance. The microenvironment in visceral organs and the skeletal system is of particular interest as a harbinger of metastatic spread. Therefore, we performed a comprehensive transcriptomic analysis of prostate cancer lung metastases with a special focus on differentially expressed genes attributable to the microenvironment. Digital gene expression analysis using the NanoString nCounter analysis system was performed on formalin-fixed, paraffin-embedded (FFPE) tissue from prostate cancer (PCa) lung metastases (n = 24). Data were compared to gene expression data from primary PCa and PCa bone metastases. Bioinformatic analysis was performed using several publicly available tools. In comparison to prostate cancer bone metastases, 209 genes were significantly upregulated, and 100 genes were significantly downregulated in prostate cancer lung metastases. Among the up-regulated genes, the top 10 genes with the most significant P-value were HLA-DPB1, PTPRC, ITGB7, C3, CCL21, CCL5, ITGAM, SERPINA1, MFAP4, ARAP2 and among the down-regulated genes, the top 10 genes with the most significant P-value were FOXC2, TWIST1, CDK14, CHAD, IBSP, EPN3, VIT, HAPLN1, SLC44A4, TBX1. In PCa lung metastases genes associated with immunogenic responses were upregulated while genes associated with epithelial-mesenchymal transition were down-regulated. We also showed that CXCR3/CXCL10 axis plays a significant role in prostate cancer lung metastases in comparison to bone metastases. In this study, we comprehensively explored transcriptomic alterations in PCa lung metastases in comparison to primary PCa and PCa bone metastases. In PCa lung metastases genes associated with immunogenic responses are upregulated while genes associated with epithelial-mesenchymal transition are down-regulated. This points to a more immunogenic phenotype of PCa lung metastases thus potentially making patients more susceptible to immunotherapeutic approaches.
转移性前列腺癌（mPCa）是一种死亡率很高的广泛疾病。揭示疾病进展的分子机制至关重要。内脏器官和骨骼系统的微环境特别受到关注，因为它预示着转移的扩散。因此，我们对前列腺癌肺转移进行了全面的转录组分析，特别关注归因于微环境的差异表达基因。使用 NanoString nCounter 分析系统对福尔马林固定、石蜡包埋（FFPE）的前列腺癌肺转移组织（n=24）进行了数字基因表达分析。将数据与原发性前列腺癌和前列腺癌骨转移的基因表达数据进行比较。使用几个公开可用的工具进行了生物信息学分析。与前列腺癌骨转移相比，前列腺癌肺转移中有 209 个基因显著上调，100 个基因显著下调。在上调的基因中，最显著的前 10 个基因的 P 值最高的是 HLA-DPB1、PTPRC、ITGB7、C3、CCL21、CCL5、ITGAM、SERPINA1、MFAP4、ARAP2；在下调的基因中，最显著的前 10 个基因的 P 值最高的是 FOXC2、TWIST1、CDK14、CHAD、IBSP、EPN3、VIT、HAPLN1、SLC44A4、TBX1。在前列腺癌肺转移中，与免疫反应相关的基因上调，而与上皮-间充质转化相关的基因下调。我们还表明，与骨转移相比，CXCR3/CXCL10 轴在前列腺癌肺转移中发挥重要作用。在这项研究中，我们全面探讨了前列腺癌肺转移与原发性前列腺癌和前列腺癌骨转移的转录组改变。在前列腺癌肺转移中，与免疫反应相关的基因上调，而与上皮-间充质转化相关的基因下调。这表明前列腺癌肺转移具有更强的免疫原性表型，因此患者可能更容易接受免疫治疗方法。
