多倍体癌细胞显示化学疗法耐药性的标志
Michael J Schmidt1, Amin Naghdloo1, Rishvanth K Prabakar1,2
1Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, California, USA.
大型多倍体癌细胞,被确定为具有增加基因组含量 (CTC-IGC) 的循环瘤细胞,与晚期前列腺癌的生存率较差有关. 与这些细胞相关的新型RNA和蛋白质标记物可能为克服化疗耐药性和预防癌症复发提供新的治疗点.
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:
- 癌症的治疗耐药性导致患者死亡率和疾病复发.
- 大型多倍体癌细胞与晚期癌症和复发有关,特别是在前列腺癌中.
- 有增加基因组含量的循环瘤细胞 (CTC-IGC) 是疾病进展的潜在指标.
研究的目的:
- 研究CTC-IGC在晚期前列腺癌患者的预后意义.
- 为了确定与多倍体癌细胞中化疗耐药性相关的分子标记物.
- 探索这些标记物的潜力,作为克服治疗耐药性的治疗标.
主要方法:
- 对44名晚期前列腺癌患者的骨髓吸血液进行分析.
- 一个单元格的副本编号对CTC-IGC.的概况.
- 单细胞DNA和RNA测序,以及用化疗治疗的诱导多倍体癌细胞 (PC3,MDA-MB-231) 上的蛋白质免疫光.
- 对公开的基因表达数据进行分析,以确定标记与复发的关联.
主要成果:
- 存在CTC-IGC与较差的无进展生存率显著相关.
- CTC-IGC显示了克隆起源,这表明完全的多化.
- 新型RNA和蛋白质标记物 (HOMER1,TNFRSF9,LRP1) 在耐化疗的多倍体细胞中被发现.
- 这些标记物在患者CTC中被发现,并与公共数据集中的复发相关.
结论:
- 包括CTC-IGC在内的大型多倍型瘤细胞在晚期前列腺癌中具有显著的预后价值.
- 这些多倍体细胞在化学疗法耐药性中起作用.
- 鉴定的RNA和蛋白质标记物为治疗癌症复发提供了潜在的新途径.
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