Comprehensive in situ co-detection of aneuploid circulating endothelial and tumor cells

Lin, Peter Ping; Gires, Olivier; Wang, Daisy Dandan; Li, Linda; Wang, Hongxia

doi:10.1038/s41598-017-10763-7

Cited by 69 publications

(130 citation statements)

References 46 publications

(81 reference statements)

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“…7B) or grouping with other types of cells such as white blood cells( Fig. 7C) and tumor cells, in line with the literature reports [11]. The binding of CTCs to leukocytes can promote their own malignant phenotype [12], but the clinical significance of CTECs and leukocyte or tumor cell agglomeration is still unclear.…”

Section: Ctec Was Not a Senescent Or Apoptotic Cell But An Active Cesupporting

confidence: 86%

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Aneuploid circulating tumor endothelial cells (CTECs) affect the detection of CTC, but they are fundamentally different

Lei¹,

Zhang²,

Liu³

et al. 2020

Preprint

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Background Aneuploidy is an important criterion for tumor cell identification. Like CTCs (circulating tumor cells), many CTECs (circulating tumor endothelial cells) have chromosomal aneuploidy. Affected by tumor microenvironment and detection method, the only identification index CD31 may not be comprehensive enough, which greatly affects the accuracy of CTCs detection. Methods Here, we explored the number distribution, expression of surface tumor markers and chromosome ploidy differences of aneuploid CTECs and CTCs in a total of 98 peripheral blood from normal volunteers, benign nodules and lung cancer patients, trying to find the differences between the two and the clinical significance of CTEC. Results We found that CTCs were mainly dominated by triploid and hyperploid (pentaploid or above), The former was mainly small CTCs, and the latter was mainly large CTCs. While the aneuploid CTECs were mostly large tetraploid cells. Combined detection of total CTC and CTEC numbers helped identify benign and malignant nodules. Furthermore, tetraploid CTC and CTEC had more obvious advantages than other ploids in identifying benign and malignant nodules. Conclusions Our findings indicated that the traditional method of distinguishing tumor and non-tumor cells by aneuploidy was not accurate. The presence of aneuploidy CTECs greatly interfered with the detection of CTCs, but they were different form CTC in cell size, chromosome ploidy distribution and had certain clinical significance. Combining CTC and CTEC had better diagnostic advantages

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Section: Ctec Was Not a Senescent Or Apoptotic Cell But An Active Cesupporting

confidence: 86%

“…First reported in 2017 [11]. In our study, aneuploid CTEC does have obvious enrichment in peripheral blood.…”

Section: Discussionsupporting

confidence: 63%

Aneuploid circulating tumor endothelial cells (CTECs) affect the detection of CTC, but they are fundamentally different

Lei¹,

Zhang²,

Liu³

et al. 2020

Preprint

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“…Therefore, developing an assay not reliant upon EpCAM for effective capture and identification of additional subtypes of CTCs is imperative. Because chromosomal instability can cause aneuploidy in human solid tumor cells, an assay integrating EpCAM‐independent subtraction and immunostaining‐fluorescence in situ hybridization (FISH) has been reported in previous studies …”

Section: Introductionmentioning

confidence: 99%

“…Because chromosomal instability can cause aneuploidy in human solid tumor cells, 18,19 an assay integrating EpCAM-independent subtraction and immunostaining-fluorescence in situ hybridization (FISH) has been reported in previous studies. 9,[20][21][22][23][24][25][26] In this study, an EpCAM-independent enrichment strategy and FISH were used to detect CTCs in lung cancer patients. 27 The relationship between CTC numbers, the levels of particular tumor markers (CEA, CA 125, CYFRA 21-1, and SCC), and the clinicopathological factors in these patients were also analyzed.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer

et al. 2019

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Background Lung cancer has the highest fatality rate of all cancer types. To improve patients’ survival and life quality, it is therefore very important to screen for and detect it at an early stage. Methods A negative enrichment–fluorescence in situ hybridization (NE‐FISH) approach was used to detect circulating tumor cells (CTCs) in lung cancer patients, and levels of lung cancer‐associated serum markers were also measured in the peripheral blood of these same patients. The correlation between CTCs, serum cancer markers (carcinoembryonic antigen [CEA], CA 125, CYFRA 21‐1, and SCC), and clinicopathological characteristics was then investigated. Moreover, the potential clinical use of the combination of CTCs and tumor markers for the diagnosis of lung cancer, especially at early stages, was also explored. Results CTC frequencies in lung cancer patients were significantly higher than in healthy control volunteers or patients with benign lung disease, and the area under the receiver operating characteristics curve for the control group was 0.846 (95% CI 0.796‐0.887, P < 0.001). The rate of CTC positivity in lung cancer patients was 68.29% when the CTC cutoff value was 2, and the sensitivity of this means of lung cancer detection rose to 82.93% by combining CTC‐based detection with measurements of serum tumor markers. Similarly, the diagnostic sensitivity of this approach in early‐stage lung cancer patients (I‐II) was improved from 63.93% to 78.69%. Detection of CTCs can thus assist with the identification of benign and malignant pulmonary nodules. Conclusions It is potentially helpful and effective to employ a combination of CTCs and serum tumor markers for the clinical diagnosis of lung cancer.

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“…In this study, we applied the subtraction enrichment (SE) and immunostaining-FISH, i•FISH ® platform for CTC detection and characterization [18,19]. Experiments were performed according to the operation manual (Cytelligen, San Diego, CA, USA).…”

Section: Immunofluorescence Staining and Se-i•fishmentioning

confidence: 99%

Circulating Tumor Cell Subtypes may Predict Responses to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Wang

et al. 2020

Preprint

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Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). However, the predictive value of circulating tumor cells (CTCs) with different molecular subtypes in NCT response has not yet been determined, which was, therefore, the aim of this study. Methods: All patients were staged as LABC and received an EC×4 –T×4 NCT regimen. Blood samples were collected from patients at the time of biopsy, and after the first and eighth NCT courses. Patients were divided into High responders (High-R) and Low responders (Low-R) according to Miller-Payne system and changes in Ki-67 levels after NCT treatment. A novel SE-i•FISH strategy was applied to detect CTCs. Subtypes were successfully analyzed in LABC patients undergoing NCT, for the first time. Results: Total CTCs increased continuously and were higher for Low-R patients; while in the High-R group, total CTCs increased slightly during NCT before returning to baseline levels. Triploid and tetraploid chromosome 8 as well as the proportion of each, increased for Low-R but not High-R patients. The number of small CTCs in the Low-R group increased significantly until the last sample, however, remained constant in the High-R group. The patients with more CTCs had shorter PFS and OS than those with less CTCs after the 8th course of NCT. Conclusions: Total CTCs as well as individual subtypes within peripheral blood following NCT were predictive of patient responses to NCT. More detailed characterization of CTC blood profiles may improve predictive capacity and lead to improved LABC treatments.

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Comprehensive in situ co-detection of aneuploid circulating endothelial and tumor cells

Cited by 69 publications

References 46 publications

Aneuploid circulating tumor endothelial cells (CTECs) affect the detection of CTC, but they are fundamentally different

Aneuploid circulating tumor endothelial cells (CTECs) affect the detection of CTC, but they are fundamentally different

Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer

Circulating Tumor Cell Subtypes may Predict Responses to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

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