在致命的前列腺癌中,糖解重编程预测预后不佳,并通过CLN6驱动治疗耐药性
Zhouda Cai1,2, Jianming Lu1, Shanshan Mo2
1State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macau, China.
Acta biochimica et biophysica Sinica
|January 13, 2026
概括
致命的前列腺癌 致命的前列腺癌
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 癌症基因组学 癌症基因组学
背景情况:
- 致死性前列腺癌的特点是瘤异质性和对雄激素受体信号抑制剂 (ARSI) 的耐药性.
- 识别疾病进展和治疗耐药性的驱动因素对于改善患者的治疗结果至关重要.
研究的目的:
- 调查糖溶解在致命前列腺癌进展和ARSI耐药性中的作用.
- 开发和验证基于糖溶解的预后得分 (GLY得分) 来进行风险分层.
主要方法:
- 单样样本基因组丰富分析 (ssGSEA) 在患者队列 (SU2C,WDCT) 上进行.
- 在HALLMARK_GLYCOLYSIS基因组上使用LASSO-Cox回归得出GLY得分.
- 在TCGA数据集和细胞系体外实验中进行了全癌症分析.
主要成果:
- 较高的葡萄糖分解活性与不良的无进展和整体存活率相关.
- GLY得分有效地在多个队伍中分层风险,并预测了更糟糕的结果.
- 在体外,抑制糖解 (2-DG) 恢复了耐药细胞系对恩扎胺的敏感性,而CLN6敲击降低了增殖.
结论:
- 葡萄糖溶解是致命前列腺癌进展和治疗耐药性的关键驱动因素.
- GLY评分在不同数据集中显示出强大的预后价值.
- 在致命的前列腺癌中,CLN6成为精准医学的潜在治疗标.
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