代谢和成像表型与前列腺癌中的RB1和TP53损失相关
Fahim Ahmad1,2,3, Margaret White1,3, Kazutoshi Yamamoto2
1Molecular Imaging Branch, NCI/NIH, Bethesda, MD-20892.
bioRxiv : the preprint server for biology
|October 1, 2025
概括
前列腺癌中RB1和TP53的丧失会改变细胞代谢,影响葡萄糖的加工和乳酸的产生. 这种代谢转变,而不仅仅是葡萄糖的吸收,可能会推动晚期前列腺癌的疾病进展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢成像 - 代谢成像
背景情况:
- 晚期前列腺癌 (PC) 治疗涉及雄激素受体 (AR) 抑制剂,但耐药性导致割抗性前列腺癌 (CRPC).
- 损失RB1,特别是TP53损失,与CRPC进展和神经内分泌前列腺癌 (NEPC) 的发展有关.
- 在渐进的CRPC中增加的18FDG-PETSUVmax表明代谢变化,但RB1/TP53失活的作用尚不清楚.
研究的目的:
- 调查RB1和/或TP53的失活是否导致前列腺癌中葡萄糖吸收增加.
- 描述与CRPC和NEPC中RB1/TP53损失相关的代谢变化.
- 评估代谢成像在区分PC亚型和预测结果方面的有用性.
主要方法:
- 使用患者衍生异种移植 (PDX) 衍生CRPC器官和割敏感PC模型.
- 进行了18FDG-PET成像,并测量了PSMA蛋白水平.
- 使用13C超极化磁共振光谱学评估代谢活动,并分析呼吸和糖解.
主要成果:
- 神经内分泌PC (NEPC) 不能仅仅通过18FDG摄入与腺癌区分;PSMA水平与表型或摄入没有相关性.
- 耐化的模型显示18FDG的摄取量较高,但比化的敏感模型更低的酸盐转化为乳酸盐.
- 通过RB1/TP53的淘汰,增加了基底呼吸和糖解,将葡萄糖转移到糖生成,并增加了乳酸脱酶的流量,而不会改变18FDG的吸收.
结论:
- RB1/TP53的失活会影响葡萄糖代谢和乳酸生产,而不仅仅是增加葡萄糖进口.
- 在CRPC中代谢异质性表明,单独用于瘤特征的18FDG吸收受到限制.
- 建议采用多模式分子成像方法,以改善晚期前列腺癌的瘤特征和患者预后.
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