在前列腺癌中,PROX1表达与ERG表达和TMPRSS2-ERG融合基因显著相关
Steven Lehrer1, Peter H Rheinstein2
1Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A.; steven.lehrer@mssm.edu.
Anticancer research
|September 26, 2025
概括
在前列腺癌中,PROX1表达与TMPRSS2-ERG融合的ERG表达有关. 向PROX1可能有助于治疗侵袭性,耐治疗性癌症.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 前列腺癌 (PCa) 呈现出血统可塑性,允许细胞逃避雄激素受体 (AR) 依赖,导致转移和治疗耐药性.
- 转录因子PROX1驱动PCa的谱系可塑性.
- TMPRSS2-ERG融合是PCa中常见的事件,与瘤的攻击性行为和ERG过度表达有关.
研究的目的:
- 研究前列腺癌中PROX1表达和ERG表达之间的关系,特别是TMPRSS2-ERG融合的背景下.
- 为了确定PROX1表达是否与ERG表达和TMPRSS2-ERG融合状态相关.
主要方法:
- 对癌症基因组图谱 (TCGA) 前列腺腺癌 (PRAD) 数据集 (n=492) 的分析.
- 使用UCSC Xena浏览器和cBioPortal进行基因表达,拷贝数修改和融合状态整合.
- 评估了基因组不稳定性,并评估了PROX1和ERG表达在融合阳性和融合阴性瘤中的相关性.
主要成果:
- 在TMPRSS2-ERG融合阳性前列腺癌中观察到PROX1和ERG表达之间的强烈正相关性 (r=0.4,p=3.2×10-16).
- 与核融合负样本相比,核融合阳性样本显示PROX1表达显著更高.
- 在TMPRSS2-ERG融合的背景下,PROX1诱导与ERG驱动的转录重编程有关.
结论:
- 在前列腺癌中,PROX1表达与ERG表达和TMPRSS2-ERG融合状态显著相关.
- PROX1 作为一个早期标记物和潜在的谱系可塑性的媒介.
- 向PROX1是一个潜在的治疗策略,用于对抗ERG融合阳性前列腺癌的可塑性驱动的进展和治疗耐药性.
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