Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

Castle, John; Morris, Karen; Pritchard, Sheila; Kirwan, Cliona C.

doi:10.1371/journal.pone.0175647

Cited by 16 publications

(17 citation statements)

References 38 publications

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“…Our findings corroborate previously published reports in terms of presence of CTCs in LC [24,25,26]. However, we were able to identify substantially more CTCs per patient without enrichment (apart of removal of RBCs) compared with published techniques where EpCAM is utilised to enrich blood samples for CTCs [27,28]. One caveat of these approaches is that EpCAM-based enrichment might miss CTCs undergoing epithelial to mesenchymal transition (EMT) [29].…”

Section: Discussionsupporting

confidence: 89%

Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications

Chudasama

Katopodis

Stone

et al. 2019

Cancers

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Background: Liquid biopsies offer a promising alternative to tissue samples, providing non-invasive diagnostic approaches or serial monitoring of disease evolution. However, certain challenges remain, and the full potential of liquid biopsies has yet to be reached. Here we report several methodological approaches to interrogate liquid biopsies using circulating tumour cell (CTC) enumeration and characterisation, transcriptomics, Raman spectroscopy, and copy number instability (CNI) scores using blood samples of lung cancer (LC) patients. Methods: We choose LC; since it still is the most common cause of cancer-related mortality worldwide, and therefore there is a need for development of new non-invasive diagnostic/prognostic technologies. Changes in gene expression were assessed using RNA-seq, and in CTCs using ImageStream, an imaging flow-cytometer. CNI scores, from paired tissue/ctDNA were also explored. Raman spectroscopy was used to provide chemical fingerprints of plasma samples. Results: CTCs were detected in all LC patients (n = 10). We observed a significant increase in CTC levels in LC patients (n = 10) compared to controls (n = 21). A similar CNI was noted in the tissue and plasma of 2 patients, where higher CNI scores corresponded with poorer outcome. Significant changes in Raman spectra (carotenoid concentrations) were noted in LC patients (n = 20) compared to controls (n = 10). RNA-seq revealed differential expression of 21 genes between LC cases and controls in both LC tissue and blood samples. Conclusions: Liquid biopsies can potentially provide a more comprehensive picture of the disease compared to a single tissue biopsy. CTC enumeration is feasible and sensitive for LC patients. Molecular profiling of CTCs is also possible from total blood. CNI scores and Raman spectra require further investigation. Further work is being undertaken to explore these methods of detection in a larger LC cohort.

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Section: Discussionsupporting

confidence: 89%

Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications

Chudasama

Katopodis

Stone

et al. 2019

Cancers

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“…The filtration-based ISET technology reported significantly higher false positive CTCs that are an order of magnitude higher compared to our result [40]. This is hardly surprising considering the large pile of cluttered cells in membrane filtration technologies for cell capture.…”

Section: Resultscontrasting

confidence: 54%

CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients

Sun

Cheng

et al. 2019

eBioMedicine

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Background The evaluation for surgical resectability of pancreatic ductal adenocarcinoma (PDAC) patients is not only imaging-based but highly subjective. An objective method is urgently needed. We report on the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of PDAC patients. Methods Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial ( E ), mesenchymal and hybrid ( H ) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification. Findings A validated multivariable model consisting of disjunctively combined CTC phenotypes: “ H -CTC≥15.0 CTCs/2ml OR E -CTC≥11.0 CTCs/2ml” generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889–1.000) and specificity of 0.886 (95% CI 0.765–0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E -CTC < 11.0 CTCs/2 ml was 16.5 months and for E -CTC ≥ 11.0 CTCs/2 ml was 5.5 months (HR = 0.050, 95% CI 0.004–0.578, P = .016). These OS results were consistent with the outcome of the metastatic analysis. Interpretation Our work suggested that H -CTC is a better predictor of metastasis and E -CTC is a significant independent predictor of OS. The CTC phenotyping model has the potential to be developed into a reliable and accurate blood test for metastatic and OS assessments of PDAC patients. Fund National Natural Science Foundation of China; Zhejiang Province Science and Technology Program; China Scholarship Council.

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“…It is also possible to misinterpret cells, like larger CD45 negative leucocytes or low number of epithelial cells, which potentially enter in blood by the peripheral intravenous cannulation. Castle et al ( 31 ) discussed also such subtype of cells, which remained to be characterized. In our previous in vitro study, we demonstrated that 54% of the BPH patients' blood samples are positive for CTCs ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

In vivo isolation of circulating tumor cells in patients with different stages of prostate cancer

et al. 2021

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Circulating tumor cells (CTCs) provide accurate information on the clinical stage of cancer progression. The present study examined the clinical validity and feasibility of a new medical device for the in vivo isolation of CTCs from the blood of patients with prostate cancer (PCa). The GILUPI CellCollector ® (DC01) was applied in 188 cases. The CTC/prostate-specific antigen (PSA) profile of each patient was checked for therapeutic monitoring of patients with PCa. The CellCollector, which is a unique in vivo approach for the isolation of CTCs, was compared with the CellSearch ® system, which is the current standard. Overall survival (OS) and diagnostic performance were evaluated. By in vivo isolation, 78.9% (56/71) of patients with metastatic disease (PCa-m) and 46.3% (24/53) of patients with localized disease (PCa-l) had ≥1 captured CTC. Kaplan-Meier analysis revealed that patients with PCa-m that had ≥5 CTCs had a significantly different OS compared with those with <5 CTCs (27.5 months vs. 37 months; HR 2.6; 95% CI 0.78–8.3). Patients with a higher number of CTCs at all time-points had the shortest median OS of 25 months (HR 1.9; 95% CI 0.4–11.6). The effectiveness of CTC isolation technologies demonstrated that in 65.7% of the applications, patients with cancer were positive for CTCs using the CellCollector. By contrast, the CellSearch system detected CTCs in 44.4% of applications. In vivo isolation of CTCs demonstrated the clinical viability of the CellCollector, related to the current standard for the isolation of CTCs from patients with PCa. The advantage of the in vivo device is that it overcomes the blood volume limitations of other CTC assays. Furthermore, the present study revealed that the CellCollector was well tolerated, and no adverse events (AEs) or serious AEs were reported.

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Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

Cited by 16 publications

References 38 publications

Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications

Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications

CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients

In vivo isolation of circulating tumor cells in patients with different stages of prostate cancer

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