骨转移(BM)前列腺癌(PCa)属于最致命的PCa形式,和治疗选择是有限的。转移的分子谱分析有助于理解定义骨转移生态位的机制。我们的目的是探索PCaBM的转录谱,并鉴定驱动进展的基因。将28个原代PCa和30个BM的石蜡包埋组织进行RNA提取并使用NanostringnCounter基因表达平台通过RNA测序进行分析。使用Nanostring™PanCancer进展小组测量总共770个癌症相关基因。基因本体论(GO),KEGG,Reactome,STRING,Metascape,PANTHER,和Pubmed用于数据整合和基因注释。与初级相比,我们在BM中鉴定了116个差异表达基因(DEG)。最重要的DEG包括CD36、FOXC2、CHAD、SPP1,MMPs,IBSP,和PTX3,它们在BM中更高的表达,和ACTG2,MYH11,CNN1,FGF2,SPOCK3和CHRDL1表达较低。DEGs在功能上与细胞外基质(ECM)蛋白聚糖有关,ECM受体,细胞-基质粘附,细胞运动以及受体酪氨酸激酶信号和对生长因子的反应。使用116DEGs的数据整合和基因注释来构建基因平台,我们将其称为“手动注释和策划的Nanostring数据平台”。总之,我们的结果强调了PCaBM中某些基因的重要性,这些基因可归因于必需的促转移功能.这项研究的数据提供了与PCaBM相关的基因的综合平台,并为进一步的研究提供了证据。
Bone metastatic (
BM) prostate cancer (PCa) belongs to the most lethal form of PCa, and therapeutic options are limited. Molecular profiling of metastases contributes to the understanding of mechanisms defining the bone metastatic niche. Our aim was to explore the transcriptional profile of PCa
BM and to identify genes that drive progression. Paraffin-embedded tissues of 28 primary PCa and 30
BM were submitted to RNA extraction and analyzed by RNA sequencing using the Nanostring nCounter gene expression platform. A total of 770 cancer-related genes were measured using the Nanostring™ PanCancer progression panel. Gene Ontology (GO), KEGG, Reactome, STRING, Metascape, PANTHER, and Pubmed were used for data integration and gene annotation. We identified 116 differentially expressed genes (DEG) in
BM compared to primaries. The most significant DEGs include CD36, FOXC2, CHAD, SPP1, MMPs, IBSP, and PTX3, which are more highly expressed in BM, and ACTG2, MYH11, CNN1, FGF2, SPOCK3, and CHRDL1, which have a lower expression. DEGs functionally relate to extracellular matrix (ECM) proteoglycans, ECM-receptors, cell-substrate adhesion, cell motility as well as receptor tyrosine kinase signaling and response to growth factors. Data integration and gene annotation of 116 DEGs were used to build a gene platform which we termed \"Manually Annotated and Curated Nanostring-data Platform\". In summary, our results highlight the significance of certain genes in PCa BM to which essential pro-metastatic functions could be ascribed. Data from this study provide a comprehensive platform of genes that are related to PCa
BM and provide evidence for further investigations.