Multiplex Gene Expression Profiling of In Vivo Isolated Circulating Tumor Cells in High-Risk Prostate Cancer Patients

Markou, Athina; Lazaridou, Marifili; Paraskevopoulos, Panagiotis; Chen, Shukun; Świerczewska, Monika; Budna, Joanna; Kuske, Andra; Gorges, Tobias M.; Joosse, Simon A.; Kroneis, Thomas; Zabel, Maciej; Sedlmayr, Peter; Alix‐Panabières, Catherine; Pantel, Klaus; Lianidou, Evi

doi:10.1373/clinchem.2017.275503

Cited by 73 publications

(71 citation statements)

References 38 publications

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“…Circulating tumor cells, which are cells shed into the bloodstream from primary tumors, recurrences, or metastases, and possess tumor-specific characteristics [10], are good targets for liquid biopsy. CTCs are considered to be an origin for metastases [11,12], and their presence has been reported for several cancers, including breast, lung, liver, and prostate cancer [13][14][15][16][17]. Recently, some researchers have reported detection rates of between 12% and 90% for EOC CTCs using different methods, including the CellSearch TM System (Veridex, Raritan, NJ), density-gradient separation followed by immunostaining of cytokeratin, and density-gradient separation combined with RT-PCR [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Monitoring the appearance and progression of tumors are important for improving the survival rate of patients with ovarian cancer. This study aims to examine circulating tumor cells (CTCs) in epithelial ovarian cancer (EOC) patients to evaluate their clinical significance in comparison to the existing biomarker CA125. Methods: Immuomagnetic bead screening, targeting epithelial antigens on ovarian cancer cells, combined with multiplex reverse transcriptase-polymerase chain reaction (Multiplex RT-PCR) was used to detect CTCs in 211 samples of peripheral blood (5 ml) from 109 EOC patients. CTCs and CA125 were measured in serial from 153 blood and 153 serum samples from 51 patients and correlations with treatment were analyzed. Immunohistochemistry was used to detect the expression of tumor-associated proteins in tumor tissues and compared with gene expression in CTCs from patients. Results: CTCs were detected in 90% (98/109) of newly diagnosed patients. In newly diagnosed patients, the number of CTCs was correlated with stage (p=0.034). Patients with stage IA-IB disease had a CTC positive rate of 93% (13/14), much higher than the CA125 positive rate of only 64% (9/14) for the same patients. The numbers of CTCs changed with treatment, and the expression of EpCAM (p=0.003) and HER2 (p=0.035) in CTCs was correlated with resistance to chemotherapy. Expression of EpCAM in CTCs before treatment was also correlated with overall survival (OS) (p=0.041). Conclusion: Detection of CTCs allows early diagnose and expression of EpCAM in CTC positive patients predicts prognosis and should be helpful for monitoring treatment.

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Section: Introductionmentioning

confidence: 99%

Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker

Zhang

et al. 2018

Cell Physiol Biochem

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“…Many groups have verified the importance of using molecular assays for CTC molecular characterization. Molecular assays based on RT‐PCR performed in nucleic acids material (RNA or genomic DNA) isolated from the EpCAM‐positive CTC fraction can give valuable information for the molecular characterization of CTC at the gene expression level, and even at the single‐cell level . Molecular assays have been also used to study the expression levels on miRNAs in CTCs, corresponding plasma and primary tumors .…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

“…Molecular assays have been also used to study the expression levels on miRNAs in CTCs, corresponding plasma and primary tumors . Especially the use of multi‐marker RT‐PCR assays can increase the sensitivity and specificity of CTCs detection and gives the ability to save precious sample and reduce the cost and time of analysis …”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

“…In a very recent study, it was shown that cell‐surface vimentin‐guided CTC enumeration may hold prognostic value and should be further validated as a possible measurement of PCa progression toward the deadly androgen‐independent form . The combination of in vivo CTC isolation with downstream RNA analysis is highly promising as a high‐throughput, specific, and ultrasensitive approach for multiplex liquid biopsy‐based molecular diagnostics for PCa patients . The clinical utility of CTC analysis in PCa is summarized in Table .…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

“…21 The successful combination of in vivo CTC isolation with downstream molecular RNA analysis is less prone to pre-analytical errors that usually result from the instability of CTCs in peripheral blood during transportation of samples to central labs for downstream CTC analysis, because the captured CTCs are immediately lysed in Trizol, where the nucleic acids are stable. 22 Size-based microfluidic devices enable CTC enrichment independently from the expression of specific antigens on their cell surface.…”

Section: Analytical Systems For Ctc Isolation Enumeration and Detmentioning

confidence: 99%

See 2 more Smart Citations

Liquid biopsies

Lianidou

Pantel

2019

Genes Chromosomes & Cancer

Self Cite

127

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Liquid biopsy is based on minimally invasive blood tests and has a high potential to significantly change the therapeutic strategy in cancer patients, providing an extremely powerful and reliable noninvasive clinical tool for the individual molecular profiling of patients in real time. Liquid biopsy approaches include the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor‐derived extracellular vesicles (EVs) that are shed from primary tumors and their metastatic sites into peripheral blood. The major advantage of liquid biopsy analysis is that it is minimally invasive, and can be serially repeated, thus allowing extracting information from the tumor in real time. Moreover, the identification of predictive biomarkers in peripheral blood that can monitor response to therapy in real time holds a very strong potential for novel approaches in the therapeutic management of cancer patients. In this review, we summarize recent knowledge on CTCs and ctDNA and discuss future trends in the field.

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Detection of circulating tumor cells in colorectal cancer patients using the GILUPI CellCollector: results from a prospective, single‐center study

et al. 2019

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The GILUPI CellCollector (CC) is a novel in vivo circulating tumor cell (CTC) detection device reported to overcome the limitations of small blood sample volumes. The aim of this prospective, blinded study was to evaluate the clinical application of the CC and to compare its performance to the CellSearch (CS) system in M0 and M1 colorectal cancer (CRC) patients. A total of 80 patients (31 M0, 49 M1) with CRC were enrolled. CTCs were simultaneously measured in the peripheral blood using CS and the CC, and the results of both assays were correlated to clinicopathological variables and overall survival. The total number of detected CTCs and CTC‐positive patients did not significantly differ between both assays. In the M0 patients, the CC detected CTCs more frequently than CS. There was no significant difference in total CTC numbers detected with the CC between M0 and M1 patients. In addition, no significant correlation with clinicopathological parameters or overall survival was observed with CC CTCs. In contrast, detection of CTCs with CS was significantly correlated with Union for International Cancer Control stage and reduced overall survival. There was no correlation between CTCs detected by the CC and the CS system. Using in silico analysis, we estimate that CC screens a volume of 0.33–18 mL during in vivo application, in contrast to much higher volumes reported elsewhere. In conclusion, while being safe and easy to use, the CC did not outperform CS in terms of CTC yield or sensitivity. While CTC detection in M0 CRC patients was significantly increased with the CC, the clinical relevance of these CTCs appears inferior to the cells identified by the CS system.

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Multiplex Gene Expression Profiling of In Vivo Isolated Circulating Tumor Cells in High-Risk Prostate Cancer Patients

Abstract: The combination of in vivo CTC isolation with downstream RNA analysis is highly promising as a high-throughput, specific, and ultrasensitive approach for multiplex liquid biopsy-based molecular diagnostics.

Cited by 73 publications

References 38 publications

Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker

Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker

Liquid biopsies

Detection of circulating tumor cells in colorectal cancer patients using the GILUPI CellCollector: results from a prospective, single‐center study

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