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前列腺癌中循环肿瘤细胞簇的检测及去分化RNA表达生存特征

Detection of CTC Clusters and a Dedifferentiated RNA-Expression Survival Signature in Prostate Cancer.

作者信息

Kozminsky Molly, Fouladdel Shamileh, Chung Jae-Seung, Wang Yugang, Smith David C, Alva Ajjai, Azizi Ebrahim, Morgan Todd, Nagrath Sunitha

机构信息

Department of Chemical Engineering University of Michigan 2300 Hayward Street Ann Arbor MI 48109 USA.

Translational Oncology Program University of Michigan 1600 Huron Pkwy Ann Arbor MI 48109 USA.

出版信息

Adv Sci (Weinh). 2018 Nov 15;6(2):1801254. doi: 10.1002/advs.201801254. eCollection 2019 Jan 23.

Abstract

Rates of progression and treatment response in advanced prostate cancer are highly variable, necessitating non-invasive methods to assess the molecular characteristics of these tumors in real time. The unique potential of circulating tumor cells (CTCs) to serve as a clinically useful liquid biomarker is due to their ability to inform via both enumeration and RNA expression. A microfluidic graphene oxide-based device (GO Chip) is used to isolate CTCs and CTC clusters from the whole blood of 41 men with metastatic castration-resistant prostate cancer. Additionally, the expression of 96 genes of interest is determined by RT-qPCR. Multivariate analyses are conducted to determine the genes most closely associated with overall survival, PSA progression, and radioclinical progression. A preliminary signature, comprising high expression of stemness genes and low expression of epithelial and mesenchymal genes, potentially implicates an undifferentiated CTC phenotype as a marker of poor prognosis in this setting.

摘要

晚期前列腺癌的进展率和治疗反应高度可变,因此需要非侵入性方法来实时评估这些肿瘤的分子特征。循环肿瘤细胞(CTC)作为一种临床上有用的液体生物标志物具有独特潜力,这是因为它们能够通过计数和RNA表达提供信息。一种基于微流控氧化石墨烯的装置(GO芯片)用于从41名转移性去势抵抗性前列腺癌男性的全血中分离CTC和CTC簇。此外,通过RT-qPCR确定96个感兴趣基因的表达。进行多变量分析以确定与总生存期、PSA进展和放射临床进展最密切相关的基因。一个初步特征,包括干性基因的高表达和上皮及间充质基因的低表达,可能意味着未分化的CTC表型是这种情况下预后不良的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7985/6343066/b12286d218a0/ADVS-6-1801254-g001.jpg

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