Improved Detection of Circulating Tumor Cells in Metastatic Colorectal Cancer by the Combination of the CellSearch® System and the AdnaTest®

Gorges, Tobias M.; Stein, Alexander; Quidde, Julia; Hauch, Siegfried; Röck, Katharina; Riethdorf, Sabine; Joosse, Simon A.; Pantel, Klaus

doi:10.1371/journal.pone.0155126

Cited by 57 publications

(46 citation statements)

References 42 publications

(46 reference statements)

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“…Firstly, CTCs that did not express EpCAM may have been excluded. EpCAM expression on CTCs has been debated, as cancer cells that undergo EMT lose EpCAM expression on the cell surface (12,21). Using flow cytometry, we have observed that the lung cancer PC-9 and H358 cell lines express EpCAM (unpublished data).…”

Section: Discussionmentioning

confidence: 92%

Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

et al. 2017

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Abstract. The detection of circulating tumor cells (CTCs) is limited by the rarity of these cells in the peripheral blood of patients with cancer. Understanding tumor biology may be useful in the development of novel therapeutic strategies for patients with lung cancer. The present study evaluated a novel size-based filtration platform for enriching CTCs from patients with lung cancer. Blood samples were obtained from 82 patients with lung cancer for CTC analysis. CTC enrichment by size-based filtration was performed on 5-ml blood samples. The collected cells were detected by immunofluorescence using monoclonal anti-human antibodies against protein tyrosine phosphatase, receptor type C (CD45) and epithelial cell adhesion molecule (EpCAM; an epithelial cell marker), as well as a DAPI nucleic acid stain. CTCs were detected in 57 patients (69.5%) using the size-based filtration platform. The mean CTC counts, defined as the number of cells with DAPI-positive, CD45-negative and EpCAM-positive staining, were 1.48±1.71 per 5 ml blood for the 66 stage I-III patients and 8.00±9.95 per 5 ml blood for the 16 stage IV patients. The presence of ≥1 CTCs per 5-ml blood sample was significantly associated with pathological stage (stage IV vs. stage I-III, P=0.009), but not with patient age or gender, tumor histology, tumor size or lymphovascular invasion. The mean CTC count of healthy donors was 0.25±0.55 per 5 ml blood. In summary, CTCs from the blood of patients with lung cancer were enriched using a size-based filtration platform and immunofluorescent staining with DAPI, CD45 and EpCAM. The CTC counts of patients with stage IV cancer were higher than those of patients with stages I-III cancer. These results suggest that this novel platform may be a useful tool for determining the prognosis of patients with lung cancer.

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Section: Discussionmentioning

confidence: 92%

Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

et al. 2017

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“…Furthermore, CTCs are barely detectable using this system in patients with non-mCRC (10). Gorges et al (19) identified CTCs using the CellSearch ® technology and/or the AdnaTest in parallel, and demonstrated that a combined analysis with both methods leads to an elevated rate of CTC detection in patients with mCRC (positive rate, 33% for CellSearch ® ; 30% for the AdnaTest;…”

Section: Discussionmentioning

confidence: 99%

Significant diagnostic value of circulating tumour cells in colorectal cancer

Hai-jiao

Zhu

et al. 2020

Oncol Lett

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Circulating tumour cells (CTCs) have potential utility in various clinical applications for cancer management. The present study focused on evaluating the diagnostic role of CTCs in colorectal cancer (CRC). A total of 89 blood samples from 59 patients diagnosed with CRC and 30 healthy individuals were collected for CTC detection. The Cyttel method is an improved CTC detection strategy, which combines negative enrichment with immunofluorescence and fluorescence in situ hybridization. This method effectively detected a significant increase in total CTCs in patients with CRC (49/59) compared with those in healthy controls (3/30). A cut-off value of 2 CTCs/3.2 ml blood yielded a sensitivity of 83.05% and a specificity of 100%. Additionally, three traditional serum tumour markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4, were examined by immunoassays. The diagnostic sensitivity of CTCs was much higher than that of CEA, CA19-9 and CA72-4 alone or in combination, particularly in patients with early stage CRC. The combined sensitivity of CTCs and CEA reached 91.53%, which was only slightly lower than the sensitivity of all four markers combined (CTCs + CEA + CA19-9 + CA72-4). CTCs with aneuploidy of chromosome 7 or 8 were carefully distinguished, and the associations among different types of CTCs, clinicopathological characteristics and overall survival were statistically analysed. Total CTCs were revealed to be significantly associated with tumour differentiation and nerve invasion. CTCs were more likely to be detected in poorly differentiated CRC tumours than in well-and moderately-differentiated tumours (P=0.026). Furthermore, to the best of our knowledge, the present study was the first to report that CTCs with multiploidy of chromosome 7 were significantly associated with TNM stage. These CTCs exhibited a high chance of being identified in the peripheral blood of patients with late-stage CRC (stage III-IV; P=0.031). The present study suggests that the combination of CTCs and CEA may serve as an effective potential diagnostic and prognostic indicator in patients with CRC. Detection of CTCs with aneuploidy may have increased specificity in predicting highly malignant and invasive tumours in CRC management.

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“…This could explain why CellSearch® and TRC methods generate much lower yields of CTC than expected. As reported previously, only 30–40% of CRC patients harbor three or more CTC per 7.5 mL of blood using the immunomagnetic CellSearch® detection system (Gorges et al ., ), and only 60% of CRC patients were shown to be positive in the CTC test with blood samples using the TRC method (Sato et al ., ). Therefore, a combined analysis of more than one gene could improve the sensitivity of CTC detection by increasing the range of CTC markers, giving an important advantage in view of the well‐known phenotypic heterogeneity of CTC.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, studies have been performed at the time of diagnosis or during initial therapy prior to disease progression using CellSearchÒ (EpCAM antigen-based) and Transcription-Reverse Transcription Concerted Reaction (TRC, CEA mRNA-based) methods. These methods have provided useful information on CRC patients (Gorges et al, 2016;Sato et al, 2012). However, due to the heterogeneity of CTC, single antigens alone, such as EpCAM or CEA, are not sufficient to capture all the CTC in blood.…”

Section: Introductionmentioning

confidence: 99%

“…In the past decade, studies on CTC have attracted great interest, and CTC value is now considered a useful marker for evaluating the tumor status, therapeutic response and prognosis of patients with multiple types of carcinoma including CRC (van Dalum et al, 2015;Hardingham et al, 2015;Lalmahomed et al, 2015). For instance, Cell SearchÒ and the TRC method have been used to measure CTC in blood samples from CRC patients (Gorges et al, 2016;Sato et al, 2012). Although these two methods are reproducible, they are both single gene-based (EpCAM-and CEA-based, respectively).…”

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confidence: 99%

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Six‐gene Assay as a new biomarker in the blood of patients with colorectal cancer: establishment and clinical validation

Shou

et al. 2019

Molecular Oncology

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Colorectal cancer ( CRC ) is the second most common cancer in men and the third most common cancer in women. Although long‐term survival has improved over the past 30 years, at least 50% of patients with CRC will develop metastases after diagnosis. In this study, we examined whether quantifying the mRNA of six CRC ‐related genes in the blood could improve disease assessment through detection of circulating tumor cells ( CTC ), and thereby improve progression prediction in relapsed CRC patients. Cell spiking assay and RT ‐ PCR were performed with blood samples from healthy volunteers spiked with six CRC cell lines to generate an algorithm, herein called the Six‐gene Assay, based on six genes ( CEA , Ep CAM , CK19 , MUC 1 , EGFR and C‐Met ) for CTC detection. The CTC s of 50 relapsed CRC patients were then respectively measured by CEA Gene Assay (single‐gene assay control) and Six‐gene Assay. Subsequently, receiver operating characteristic analysis of the CTC panel performance in diagnosing CRC was conducted for both assays. Moreover, the 2‐year progression‐free survival ( PFS ) of all patients was collected, and the application of CEA Gene Assay and Six‐gene Assay in predicting PFS was carefully evaluated with different CTC cutoff values. Encouragingly, we successfully constructed the first multiple gene‐based algorithm, named the Six‐gene Assay, for CTC detection in CRC patients. Six‐gene Assay was more sensitive than CEA Gene Assay; for instance, in 50 CRC patients, the positive rate of Six‐gene Assay in CTC detection was 82%, whereas that of CEA Gene Assay was only 70%. Moreover, Six‐gene Assay was more sensitive and accurate than CEA Gene Assay in diagnosing CRC as well as predicting the 2‐year PFS of CRC patients. Statistical analysis demonstrated that CTC numbers measured by Six‐gene Assay were significantly associated with 2‐year PFS . This novel Six‐gene Assay improves the definition of disease status and correlates with PFS in relapsed CRC , and thus holds promise for future clinical applications.

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Improved Detection of Circulating Tumor Cells in Metastatic Colorectal Cancer by the Combination of the CellSearch® System and the AdnaTest®

Cited by 57 publications

References 42 publications

Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Significant diagnostic value of circulating tumour cells in colorectal cancer

Six‐gene Assay as a new biomarker in the blood of patients with colorectal cancer: establishment and clinical validation

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