综合单细胞转录基因分析确定了一种与前列腺癌进展有关的新型血统可塑性相关的癌细胞类型
Faming Zhao1, Tingting Zhang2, Jinlan Wei2
1School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China; Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
EBioMedicine
|October 17, 2024
概括
研究人员发现了一种新的前列腺癌细胞群 (LPCs),与不良结果有关. 这些细胞表现出较低的雄激素受体活性和高的HMMR表达,驱动侵略性疾病和神经内分泌表型.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
背景情况:
- 癌细胞的可塑性使瘤适应和抵抗.
- 在前列腺癌 (PCa) 中,可塑性往往导致治疗耐药性和神经内分泌分化.
- 识别与可塑性相关的癌细胞至关重要,但具有挑战性.
研究的目的:
- 开发一种基因特征,用于识别前列腺癌中的血统可塑性.
- 发现和描述一种具有血统可塑性的前列腺癌细胞的新型群体.
- 验证这些细胞在疾病进展和患者预后中的作用.
主要方法:
- 整合了13个人类PCa批量转录基因队列和9个实验模型数据集,以创建与血统可塑性相关的基因签名 (LPSig).
- 在10个scRNA-seq数据集 (222,529个细胞) 的元图表上应用AUCell丰富分析,以识别与可塑性相关的细胞 (LPC).
- 通过使用额外的scRNA-seq数据,多重免疫组织化学,体外/体外实验,qPCR和西欧涂料验证的结果.
主要成果:
- 在PCa中,LPSig准确地捕获了瘤谱系可塑性动态.
- 鉴定出了一种与血统可塑性相关的PCa细胞 (LPCs) 的新型少数群体.
- LPCs在PCa转差,复发和低生存率中发挥关键作用,表达高HMMR和低雄激素受体 (AR) 活性.
- 鉴定出HMMR是LPC的细胞表面标记物,它对于侵略性特征和NE表型而言是必不可少的.
结论:
- 在PCa中发现了一种新的LPC群体,其特点是AR活性较低,茎状特征和HMMR升高.
- 这些LPC与前列腺癌的预后不佳有关.
- HMMR作为一个潜在的治疗目标,攻击性PCa.
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