Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Zheng, Xizhong; Фан, Ли; Zhou, Pengfei; Ma, Hong; Huang, Shao-Yi; Yu, Dandan; Zhao, Lei; Yang, Shengli; Li, Jun; Huang, Ai; Cai, Congli; Dai, Xiaomeng; Zhang, Tao

doi:10.1016/j.tranon.2017.02.007

Cited by 39 publications

(34 citation statements)

References 51 publications

(70 reference statements)

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“…The pioneer ISET‐GAC study evaluated patients from China (45 nonmetastatic and 41 metastatic cases) and, perhaps because of differences in study design and ethnicity, the authors report a much lower CTC detection rate in nonmetastatic cases (52%) versus the 90% detection rate in our study. However, despite this difference, these authors conclude (and our findings give support to this concept) that for most GAC cases, cell invasion and entry of cancer cells into the bloodstream occurs in the early stages of the disease, which probably justifies the high rates of distant recurrence and the overall poor prognosis of this disease.…”

Section: Discussionsupporting

confidence: 53%

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

et al. 2019

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Background Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data. Materials and Methods CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples). Results A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2‐negative primary tumors but HER2‐positive CTCs. A significant CTC count drop in follow‐up was seen for CTC‐HER2‐positive cases (4.45 to 1.0 CTCs per mL) compared with CTC‐HER2‐negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC‐plakoglobin‐positive cases (2.9 to 1.25 CTCs per mL). Conclusion CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC. Implications for Practice The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment.

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Section: Discussionsupporting

confidence: 53%

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

et al. 2019

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“…On the other hand, the challenge of CTC single cell analysis could be attenuated by detecting CTC clusters or circulating tumor microembolies (CTM) instead of single CTCs. Using isolation by size of epithelial tumor cells (ISET), a technology based on differences in the size and shape of cancer cells and normal blood cells, Zheng et al [60] efficiently detected CTCs/CTM in GC patients. CTM positivity, which was correlated with serum CA125 level, was an independent predictor of PFS and OS of stage IV patients.…”

Section: Future Perspectivementioning

confidence: 99%

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Huong

Gurshaney

Bình

et al. 2020

Cancers

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With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

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“…The presence and high numbers of CTC clusters have been demonstrated, and is associated with a poor prognosis in patients with gastric cancer. CTC clusters are considered to possess a higher metastatic potential compared with single CTCs (31). Therefore, CTC clusters may also serve as biomarkers for indicating cancer prognosis and monitoring cancer metastasis.…”

Section: Ctc Count --------------------------------------------------mentioning

confidence: 99%

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

Xue

Ren

et al. 2020

Oncol Rep

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Circulating tumor cells (CTCs) or CTC clusters are considered as suitable and relevant targets for liquid biopsy as they more accurately indicate cancer progression, the therapeutic effects of treatment and allows for monitoring of cancer metastasis in real-time. Among the various methods for isolating CTCs, size-based filtration is one of the most convenient methods. However, cell clogging makes the filtration process less efficient. In the present study, an electromagnetic vibration-based filtration (eVBF) device was developed that efficiently isolated rare CTCs and CTC clusters from clinical blood samples of patients with gastric cancer. Using human blood samples spiked with human gastric cancer cells, the parameters of this device such as vibrating amplitude and flow rate were optimized. Putative CTCs were detected using a conventional filtration method and the eVBF device from the peripheral blood samples of patients with gastric cancer. Continuous flow isolation of CTCs was evaluated by a simulated blood flow system. The eVBF device utilized the electromagnetic force to generate a periodic vibration that prevented the cell clogging and improved the filtering efficiency. The optimized eVBF device with the high-amplitude vibration exhibited a recovery efficiency of 80-90% from whole blood samples spiked with 100 or 1,000 gastric cancer cells per ml. Using the eVBF device, CTCs were detected in 100% of patients (10/10) with gastric cancer, and the positive detection rate of the eVBF device was 30% higher compared with the conventional filtration method. Furthermore, CTC clusters were detected in 40% (4/10) of CTC-positive patient samples, and the integrity of CTC clusters was preserved using the eVBF device. The eVBF device allowed for high-throughput (1 ml/min) and continuous flow isolation of CTCs without the addition of any antibodies, any chemical reagents or any pretreatment processes. Thus, the eVBF device provides an efficient tool for isolating rare CTCs and CTC clusters from patients with cancer, highlighting its potential for use in cancer diagnosis, treatment and cancer biology research.

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Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Cited by 39 publications

References 51 publications

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Emerging Role of Circulating Tumor Cells in Gastric Cancer

High‑throughput and continuous flow isolation of rare circulating tumor cells and clusters in gastric cancer from human whole blood samples using electromagnetic vibration‑based filtration

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