Dataset Information

Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis.

ABSTRACT: Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample. Cytochalasin B (CB) treatment promotes cells to release large number of EVs from their surface, as demonstrated by CB-treated cells (5 µg/mL for 3 h) secreting 3.5-fold more EVs, compared to the non-treated cells. CB further generates 1.7-fold more EVs from the cells captured on our CTC filtration device (the fabric filter), compared to those from the cell culture flasks, owing to its multiple pore structure design which reduces the non-specific binding of EVs. Both CB-treated cancer cells and CB-induced EVs are found to overexpress tumor-associated markers, demonstrating a potential for the development of CTC dual-screening platform. Collectively, the results presented in this study reveal that our multi-modal cancer screening platform can synergistically improve the reliability and efficacy of the current CTC analysis systems.

SUBMITTER: Bu J

PROVIDER: S-EPMC6856233 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis.

Bu Jiyoon J Shim Jae-Eul JE Lee Tae Hee TH Cho Young-Ho YH

Nano convergence 20191115 1

Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample ...[more]

PMID: 31728677

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Project description:Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score?4+4 prostate cancer (PCa) in a manner independent of PSA.Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy.PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score?8 disease, a high-risk prognostic factor, from patients with Gleason Score?7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients.PMP enumeration was able to identify patients with Gleason Score ?8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Project description:Extracellular vesicles (EVs) are abundantly released into the systemic circulation, where they show remarkable stability and harbor molecular constituents that provide biochemical information about their cells of origin. Due to this characteristic, EVs are attracting increasing attention as a source of circulating biomarkers for cancer liquid biopsy and personalized medicine. Despite this potential, none of the discovered biomarkers has entered the clinical practice so far, and novel approaches for the label-free characterization of EVs are highly demanded. In this regard, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides a quick, reproducible, and informative biomolecular fingerprint of EVs. In this pilot study, we investigated, for the first time in the literature, the capability of FTIR spectroscopy to distinguish between EVs extracted from sera of cancer patients and controls based on their mid-IR spectral response. For this purpose, EV-enriched suspensions were obtained from the serum of patients diagnosed with Hepatocellular Carcinoma (HCC) of nonviral origin and noncancer subjects. Our data point out the presence of statistically significant differences in the integrated intensities of major mid-IR absorption bands, including the carbohydrate and nucleic acids band, the protein amide I and II bands, and the lipid CH stretching band. Additionally, we used Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) for the automated classification of spectral data according to the shape of specific mid-IR spectral signatures. The diagnostic performances of the proposed spectral biomarkers, alone and combined, were evaluated using multivariate logistic regression followed by a Receiving Operator Curve analysis, obtaining large Areas Under the Curve (AUC = 0.91, 95% CI 0.81–1.0). Very interestingly, our analyses suggest that the discussed spectral biomarkers can outperform the classification ability of two widely used circulating HCC markers measured on the same groups of subjects, namely alpha-fetoprotein (AFP), and protein induced by the absence of vitamin K or antagonist-II (PIVKA-II).

Dataset Information

Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis.

Publications

Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis.

Similar Datasets

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