空间基因组学将热休克蛋白鉴定为与前列腺癌脂肪前列腺周围间隙浸润相关的关键分子变化。
Spatial Genomics Identifies Heat Shock Proteins as Key Molecular Changes Associated to Adipose Periprostatic Space Invasion in Prostate Cancer.
作者信息
Cussenot Olivier, Poupel Lucie, Mousset Coralie, Lavergne Julien, Bruyere Franck, Fontaine Alix, Cancel-Tassin Géraldine, Fromont-Hankard Gaelle
机构信息
Department of Urology, Medical University of Vienna, 1090 Vienna, Austria.
CeRePP, 75020 Paris, France.
出版信息
Cancers (Basel). 2024 Dec 24;17(1):2. doi: 10.3390/cancers17010002.
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.
目的
利用前列腺癌细胞的空间转录组分析来鉴定前列腺癌侵袭脂肪组织空间过程中的分子变化。
方法
本研究对从pT3a病理分期的根治性前列腺切除术中获取的前列腺内和前列腺外配对样本进行。
结果
差异基因表达显示，来自前列腺周围脂肪组织空间的前列腺癌泛细胞角蛋白阳性（PanCK+）细胞中，热休克蛋白基因DNAJB1、HSPA8、HSP90AA1、HSPA1B、HSPA1A上调。前列腺外扩展与参与转移扩散的基因（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（PSMA，即FOLH1）的过表达显著相关。它们与6号染色体长臂、10号染色体长臂、16号染色体长臂缺失以及8号染色体24区带增益有关。
结论
前列腺癌侵袭脂肪组织的包膜外扩展诱导了与热休克蛋白相关的适应性过程；包膜外扩展中的前列腺癌细胞还呈现出ERG非依赖性侵袭性、雄激素受体共激活以及特定拷贝数变异变化的转录组特征。
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