Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics

利用惯性微流控技术从前列腺癌患者精液中分离循环肿瘤细胞

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作者:Alexey S Rzhevskiy, Alina Y Kapitannikova, Steven A Vasilescu, Tamilla A Karashaeva, Sajad Razavi Bazaz, Mark S Taratkin, Dmitry V Enikeev, Vladimir Y Lekarev, Evgeniy V Shpot, Denis V Butnaru, Sergey M Deyev, Jean Paul Thiery, Andrei V Zvyagin, Majid Ebrahimi Warkiani

Abstract

Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min-1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

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