Biology and clinical significance of circulating tumor cell subpopulations in lung cancer

O’Flaherty, Linda; Wikman, Harriet; Pantel, Klaus

doi:10.21037/tlcr.2017.07.03

Cited by 30 publications

(29 citation statements)

References 97 publications

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“…But what are the similarities between CTCs and primary tumors tissues? Studies have investigated the similarities and differences between CTCs and primary tumors [13]. We found that CTCs may be the same or different from primary tumor tissue, but we failed to reach a conclusion as we had few samples, thus, in the future we need to increase our sample size to identify the relevant factors explaining the differences between tissues and CTCs.…”

Section: Discussionmentioning

confidence: 84%

“…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%

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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: Discussionmentioning

confidence: 84%

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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“…CellSearch ® has established clinically prognostic value in a variety of cancers, yet it does not detect and even excludes certain circulating cancer-associated cells [69]. Other CTC isolation techniques (e.g., microfilters based on size [70]) allow additional phenotypic analysis and identification of other potentially relevant circulating cancer-associated cells, including cells that have undergone epithelial-mesenchymal transition (EMT) and down-regulated EpCAM, or which express myeloid/macrophage-markers CD45/14+ [4,5,8,27,28,71,72].…”

Section: Fusion Cell Detection In the Peripheral Blood Of Cancer Patimentioning

confidence: 99%

Tumor-Cell–Macrophage Fusion Cells as Liquid Biomarkers and Tumor Enhancers in Cancer

Manjunath

Porciani

Mitchem

et al. 2020

IJMS

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Although molecular mechanisms driving tumor progression have been extensively studied, the biological nature of the various populations of circulating tumor cells (CTCs) within the blood is still not well understood. Tumor cell fusion with immune cells is a longstanding hypothesis that has caught more attention in recent times. Specifically, fusion of tumor cells with macrophages might lead to the development of metastasis by acquiring features such as genetic and epigenetic heterogeneity, chemotherapeutic resistance, and immune tolerance. In addition to the traditional FDA-approved definition of a CTC (CD45-, EpCAM+, cytokeratins 8+, 18+ or 19+, with a DAPI+ nucleus), an additional circulating cell population has been identified as being potential fusions cells, characterized by distinct, large, polymorphonuclear cancer-associated cells with a dual epithelial and macrophage/myeloid phenotype. Artificial fusion of tumor cells with macrophages leads to migratory, invasive, and metastatic phenotypes. Further studies might investigate whether these have a potential impact on the immune response towards the cancer. In this review, the background, evidence, and potential relevance of tumor cell fusions with macrophages is discussed, along with the potential role of intercellular connections in their formation. Such fusion cells could be a key component in cancer metastasis, and therefore, evolve as a diagnostic and therapeutic target in cancer precision medicine.

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“…It has been well documented that the commonly available serum tumor biomarkers for provides little diagnostic value for early lung cancer diagnosis (7)(8)(9)(10)(11)(12)(13). CACs occur early in tumorigenesis and might be of use as a biomarker for lung cancer (21,22).…”

Section: Discussionmentioning

confidence: 99%

“…The current early detection methods for lung cancer are not su cient. Indeed, available biomarkers (like carcinoembryonic antigen) and circulating nucleic acids have a low sensitivity (7)(8)(9). Plain X-ray, computed tomography (CT), and positron-emission tomography (PET)/CT have relatively high rates of false-positive and have low sensitivity for tumors < 10 mm and pure ground-glass nodules (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Detection of circulating genetically abnormal cells using 4-color fluorescence in situ hybridization for the early detection of lung cancer

Feng

Ye²,

et al. 2020

Preprint

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Background Available biomarkers lack sensitivity for early lung cancer. Circulating genetically abnormal cells (CACs) occur early in tumorigenesis. To determine the diagnostic value of CACs in blood detected by 4-color fluorescence in situ hybridization (FISH) for lung cancer. Methods This was a prospective study of patients with pulmonary nodules ≤ 30 mm detected between 10/2019 and 01/2020 at four tertiary hospitals in China. All patients underwent a pathological examination of lung nodules found by imaging and were grouped as malignant and benign. CACs were detected by 4-color FISH. Patients were divided into the training and validation cohorts. Receiver operating characteristics analysis was used to analyze the diagnosis value of CACs. Results A total of 205 participants were enrolled. Using a cut-off value of ≥ 3, blood CACs achieved areas under the curve (AUCs) of 0.887, 0.823, and 0.823 for lung cancer in the training and validation cohorts, and all patients, respectively. CACs had high diagnostic values across all tumor sizes and imaging lesion types. CACs were decreased after surgery (median, 4 vs. 1, P < 0.001) in the validation set. The CAC status between blood and tissues was highly consistent (kappa = 0.909, P < 0.001). The AUC of CAC (0.823) was higher than that of CEA (0.478), SCC (0.516), NSE (0.506), ProGRP (0.519), and CYFRA21-1 (0.535) (all P < 0.001). Conclusions CACs might have a high value for the early diagnosis of lung cancer. These findings might need to be validated in future studies. Evidence suggested homology in genetic aberrations between the CACs and the tumor cells.

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Biology and clinical significance of circulating tumor cell subpopulations in lung cancer

Cited by 30 publications

References 97 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

Tumor-Cell–Macrophage Fusion Cells as Liquid Biomarkers and Tumor Enhancers in Cancer

Detection of circulating genetically abnormal cells using 4-color fluorescence in situ hybridization for the early detection of lung cancer

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