Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients

Pan, Ruijun; Hao, Hong; Sun, Jing Ping; Yu, Chaoran; Liu, Hai-Shan; Li, Peiyong; Zheng, Min

doi:10.2147/cmar.s300554

Cited by 26 publications

(21 citation statements)

References 37 publications

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“…The clinical utility of identifying circulating tumour cells in colorectal cancer patients has already been described by several authors [ 15 , 22 , 23 , 25 , 27 , 38 , 39 ]. However, current protocols for the isolation and characterisation of CTCs are mainly limited to the microscopic evaluation of one or two markers, compromising the ability to identify different CTC subpopulations.…”

Section: Discussionmentioning

confidence: 99%

“…We defined CTCs as cells expressing cytokeratin (either bound to IsoFlux TM beads or not, as we pre-treated samples with papain to facilitate their analysis). Cut-off values of CTCs in non-metastatic colorectal cancer have been defined as between 1 and 5 cells in different studies [ 23 , 25 , 38 , 39 ]. However, as our methodology is more sensitive and efficient, we detected more CTCs per patient, and thus, cut-off values could be slightly elevated.…”

Section: Discussionmentioning

confidence: 99%

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Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream)

Ruiz-Rodríguez

Molina-Vallejo

Aznar-Peralta

et al. 2021

Cancers

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The isolation of circulating tumour cells (CTCs) in colorectal cancer (CRC) mostly relies on the expression of epithelial markers such as EpCAM, and phenotypic characterisation is usually performed under fluorescence microscopy with only one or two additional markers. This limits the ability to detect different CTC subpopulations based on multiple markers. The aim of this work was to develop a novel protocol combining two platforms (IsoFluxTM and ImageStream®X) to improve CTC evaluation. Cancer cell lines and peripheral blood from healthy donors were used to evaluate the efficiency of each platform independently and in combination. Peripheral blood was extracted from 16 early CRC patients (before loco-regional surgery) to demonstrate the suitability of the protocol for CTC assessment. Additionally, peripheral blood was extracted from nine patients one month after surgery to validate the utility of our protocol for identifying CTC subpopulation changes over time. Results: Our protocol had a mean recovery efficiency of 69.5% and a limit of detection of at least four cells per millilitre. We developed an analysis method to reduce noise from magnetic beads used for CTC isolation. CTCs were isolated from CRC patients with a median of 37 CTCs (IQ 13.0–85.5) at baseline. CTCs from CRC patients were significantly (p < 0.0001) larger than cytokeratin (CK)-negative cells, and patients were stratified into two groups based on BRAFV600E and PD-L1 expression on CK-positive cells. The changes observed over time included not only the number of CTCs but also their distribution into four different subpopulations defined according to BRAFV600E and PD-L1 positivity. We developed a novel protocol for semi-automatic CTC isolation and phenotypic characterisation by combining two platforms. Assessment of CTCs from early CRC patients using our protocol allowed the identification of two clusters of patients with changing phenotypes over time.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream)

Ruiz-Rodríguez

Molina-Vallejo

Aznar-Peralta

et al. 2021

Cancers

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“…It was reported that high CTC counts correlated significantly with increased tumor stage with differences observed in T stage and N stages of the left and right hemicolon cancer. Furthermore, high CTC counts correlated with high tumor recurrence rate and worse prognosis indicating that change in CTCs counts could serve as a valuable tool for CRC prognosis [ 157 ]. Similarly, dynamic monitoring of CTC counts as a prognostic tool was investigated in a prospective phase II trial on153 CRC patients with resectable liver metastasis (LM).…”

Section: Introductionmentioning

confidence: 99%

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

Raza

Khan

Inchakalody

et al. 2022

J Exp Clin Cancer Res

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Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and limited applicability in longitudinal monitoring, liquid biopsy has gathered immense attention in CRC. Liquid biopsy has several advantages over tissue biopsy including ease of sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Furthermore, the importance of liquid biopsy is signified by approval of several liquid biopsy assays by regulatory bodies indicating the powerful approach of liquid biopsy for comprehensive CRC screening, diagnostic and prognostics. Several liquid biopsy biomarkers such as novel components of the microbiome, non-coding RNAs, extracellular vesicles and circulating tumor DNA are extensively being researched for their role in CRC management. Majority of these components have shown promising results on their clinical application in CRC including early detection, observe tumor heterogeneity for treatment and response, prediction of metastases and relapse and detection of minimal residual disease. Therefore, in this review, we aim to provide updated information on various novel liquid biopsy markers such as a) oral microbiota related bacterial network b) gut microbiome-associated serum metabolites c) PIWI-interacting RNAs (piRNAs), microRNA(miRNAs), Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and d) circulating tumor DNAs (ctDNA) and circulating tumor cells (CTC) for their role in disease diagnosis, prognosis, treatment monitoring and their applicability for personalized management of CRC.

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“…Meanwhile, Sebastian Hinz et al revealed that they used Ficoll extraction of mononuclear cells followed by CK20 RT–PCR to detect CTCs, with a detection rate of 30% [ 32 ]. In other investigations, CTCs were detected in almost 45% of CRC patients (TNM stage I–IV) [ 33 , 34 ]. Different detection methods may have different detection rates; nevertheless, standardized methods and novel techniques will enhance CTC detection in early malignancies [ 35 ].…”

Section: Main Textmentioning

confidence: 92%

Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer

et al. 2022

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Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called “liquid biopsy” has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.

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Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients

Cited by 26 publications

References 37 publications

Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream)

Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream)

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer

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