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单细胞转录组学确定PDIA4是多发性骨髓瘤进展和治疗脆弱性的标志物

Wenjie Yu¹, Jiamin Zhan¹, Yanxia Wang¹

¹Institute of Hematology, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China.

Journal of translational medicine

|October 22, 2025

概括

蛋白二硫化异构酶A4 (PDIA4) 对于多发性骨髓瘤 (MM) 细胞生存和进展至关重要. 向PDIA4可能会提高治疗效率,并克服对蛋白酶体抑制剂等疗法的耐药性.

科学领域:

血液瘤学血液瘤学
分子生物学分子生物学
癌症基因组学癌症基因组学

背景情况:

多发性骨髓瘤 (MM) 是一种具有不完全理解的转录调节的血细胞恶性瘤.
驱动MM进展和生存的关键机制需要进一步阐明.

研究的目的:

描述MM中血细胞分化的转录格局.
为了确定参与MM病原和生存的新基因和途径.

主要方法:

综合单细胞RNA测序 (scRNA-seq) 来自健康的捐赠者和MM患者 (MGUS,SMM,NDMM).
伪化和丰富分析以确定关键基因.
使用MMRF CoMMpass队列进行预测验证.
在体外和体内生物功能研究.

主要成果:

确定PDIA4是一种终端状态的血细胞基因,在MM中表达上调.
高PDIA4表达与MM患者的整体存活率差相关.
PDIA4的枯竭激活了UPR,损害了增殖,并使MM细胞对博尔特佐米布敏感.
在体内,PDIA4抑制抑制了瘤生长.

结论:

PDIA4是展开蛋白质反应 (UPR) 和MM细胞存活的关键调节者.
针对PDIA4是一个潜在的策略,可以提高蛋白酶体抑制剂的疗效,克服MM的治疗耐药性.

关键词:

多发性骨髓瘤是一种多发性骨髓瘤.在PDIA4中,PDIA4是指PDIA4.预后标志物是一个预后标志物.单细胞RNA测序的一个细胞.

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