文章：

空间基因组学揭示热休克蛋白为前列腺癌脂肪周间隙侵袭的关键分子变化

Spatial Genomics Identifies Heat Shock Proteins as Key Molecular Changes Associated to Adipose Periprostatic Space Invasion in Prostate Cancer

原文发布日期：24 December 2024

DOI: 10.3390/cancers17010002

类型: Article

开放获取: 是

英文摘要：

Purpose: To identify molecular changes during PCa invasion of adipose space using Spatial Transcriptomic Profiling of PCa cells. Methods: This study was performed on paired intraprostatic and extraprostatic samples obtained from radical prostatectomy with pT3a pathological stages. Results: Differential gene expression revealed upregulation of heat shock protein genes: DNAJB1, HSPA8, HSP90AA1, HSPA1B, HSPA1A in PCa PanCK+ cells from the adipose periprostatic space. Extraprostatic extension was significantly associated with overexpression of genes involved in metastatic spread (EGR1, OR51E2, SPON2), of aggressiveness ERG negative signature of enhancers of androgen receptor (HOXB13, FOXA1), and of PSMA (FOLH1). They were associated with loss at 6q, 10q, 16q, and gain at 8q24 locus. Conclusions: PCa invasion of adipose EPE induces adaptative process related to heat shock proteins; PCa cells in EPE also present transcriptomics signatures for ERG independent aggressiveness, androgen receptor co-activation, and specific CNV changes.

摘要翻译： 

目的：利用前列腺癌细胞的空间转录组学分析，识别前列腺癌侵犯脂肪间隙过程中的分子变化。方法：本研究采用根治性前列腺切除术中获取的pT3a病理分期配对样本，包括前列腺内及前列腺外组织。结果：差异基因表达分析显示，来自前列腺周围脂肪间隙的前列腺癌PanCK+细胞中热休克蛋白基因（DNAJB1、HSPA8、HSP90AA1、HSPA1B、HSPA1A）表达上调。前列腺外扩展与转移相关基因（EGR1、OR51E2、SPON2）、雄激素受体增强子的侵袭性ERG阴性特征基因（HOXB13、FOXA1）以及前列腺特异性膜抗原基因（FOLH1）的过表达显著相关。这些变化与6q、10q、16q位点的缺失及8q24位点的扩增相关。结论：前列腺癌侵犯脂肪性前列腺外扩展会诱导与热休克蛋白相关的适应性过程；同时，前列腺外扩展中的前列腺癌细胞还表现出ERG非依赖性侵袭特征、雄激素受体共激活特征以及特定的拷贝数变异改变。

原文链接：

Spatial Genomics Identifies Heat Shock Proteins as Key Molecular Changes Associated to Adipose Periprostatic Space Invasion in Prostate Cancer