前列腺癌肺转移的综合转录组分析。
Comprehensive transcriptomic analysis of prostate cancer lung metastases.
发表日期:2024
作者:
Alireza Saraji, Katharina Wulf, Janine Stegmann-Frehse, Duan Kang, Anne Offermann, Danny Jonigk, Mark Philipp Kuehnel, Jutta Kirfel, Sven Perner, Verena Wilbeth Sailer
来源:
GENES & DEVELOPMENT
摘要:
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中的微环境作为转移扩散的先兆而受到特别关注。因此,我们对前列腺癌肺转移进行了全面的转录组分析,特别关注微环境引起的差异表达基因。使用 NanoString nCounter 分析系统对来自前列腺癌 (PCa) 肺转移 (n = 24) 的福尔马林固定石蜡包埋 (FFPE) 组织进行数字基因表达分析。将数据与原发性 PCa 和 PCa 骨转移的基因表达数据进行比较。使用几种公开可用的工具进行生物信息分析。与前列腺癌骨转移相比,前列腺癌肺转移中有209个基因显着上调,100个基因显着下调。在上调基因中,P值最显着的前10位基因是HLA-DPB1、PTPRC、ITGB7、C3、CCL21、CCL5、ITGAM、SERPINA1、MFAP4、ARAP2;在下调基因中,P值最高的10个基因是HLA-DPB1、PTPRC、ITGB7、C3、CCL21、CCL5、ITGAM、SERPINA1、MFAP4、ARAP2 P 值最显着的 10 个基因是 FOXC2、TWIST1、CDK14、CHAD、IBSP、EPN3、VIT、HAPLN1、SLC44A4、TBX1。在PCa肺转移中,与免疫原性反应相关的基因上调,而与上皮间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着重要作用。在这项研究中,我们全面探讨了 PCa 肺转移与原发性 PCa 和 PCa 骨转移相比的转录组变化。在PCa肺转移中,与免疫原性反应相关的基因上调,而与上皮间质转化相关的基因下调。这表明 PCa 肺转移具有更高的免疫原性表型,因此可能使患者更容易接受免疫治疗方法。版权所有:© 2024 Saraji 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
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.Copyright: © 2024 Saraji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.