Predictive and prognostic value of circulating tumor cell detection in lung cancer: A clinician's perspective

Tognela, Annette; Spring, Kevin; Becker, Therese M.; Caixeiro, Nicole J.; Bray, Victoria; Yip, Po Yee; Chua, Wei; Lim, Stephanie; Souza, Paul de

doi:10.1016/j.critrevonc.2014.10.001

Cited by 32 publications

(28 citation statements)

References 90 publications

(151 reference statements)

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“…22 Consequently, "liquid biopsy" has been used for isolation and characterization of CSCs in almost all cancers as it has the potential to be used for frequent genetic analysis of tumor diagnosis/prognosis, in personalized therapy selection and provides considerable leverage of being detected at any tumor stage. [7][8][9]23 CTCs hold much more genetic/molecular information than free-circulating nucleic acid and proteins, thus revealing the importance of inter-cell heterogeneity in correlating cancer prognosis and treatment resistance. 24 However, CTCs are rare in the peripheral blood and tend to form aggregates, and because of their low concentration, there is limited study on the biology of CTCs.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] Hence, sensitive isolation and insightful molecular characterization of CTCs could assist as a "liquid biopsy" and aid to improve individual treatment regimens for cancer patients; however, reproducible and accurate methods for identifying and segregating CTCs have remained a challenge. [7][8][9] Till date, epithelial cell surface markers are being used as a sole modality for isolation of rare population of CTCs by various systems. [10][11][12][13][14] Utilizing these markers for the effective isolation of CTCs may provide erroneous results as they result in the down-regulation of epithelial cell markers during the epithelial-mesenchymal transition (EMT).…”

Section: Introductionmentioning

confidence: 99%

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Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

2017

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Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(−) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

2017

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“…Circulating tumor cells (CTCs) refer to the tumor cells circulating in the peripheral blood; they either spontaneously or as a result of clinical operations spread from the solid tumor’s primary focus or metastatic focus [9]. Studies have shown that CTCs correlate with metastatic lymph nodes and can help to show prognosis of various cancers [10–12].…”

Section: Introductionmentioning

confidence: 99%

Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China

Zhang

Niu

et al. 2017

Med Sci Monit

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BackgroundBreast cancer (BC) is the most common malignant tumor in females. This study investigated the role and utility of CTC monitoring in evaluating the prognosis of triple-negative breast cancer patients.Material/MethodsWe enrolled 286 female triple-negative breast cancer patients who were diagnosed at and received radical resection surgery in our hospital. Peripheral venous blood samples were collected preoperatively and at 3 and 7 days postoperative, and the Cell Search system was used to detect CTC in peripheral blood. We analyzed the relationship between preoperative CTC level and clinical pathological characteristics of patients. Kaplan-Meier method was used to establish progression-free survival curves and overall survival curves, we used the log-rank test to compare the survival rate, and we explored the effects of preoperative and postoperative CTC levels on patient survival.ResultsCompared with preoperative levels, the average CTC content in peripheral blood of breast cancer patients was significantly increased at 3 days after surgery, and then decreased to the preoperative baseline level by 7 days after surgery. The 3-year overall survival rate and progression-free survival rate in patients with CTC >5/7.5 mL peripheral blood were significantly lower than in patients with CTC <5/7.5 mL peripheral blood detected preoperatively and at 3 and 7 days postoperatively.ConclusionsDynamic monitoring of preoperative and postoperative CTC levels can accurately predict recurrence and progression of disease, and is important in postoperative monitoring and prognosis evaluation.

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“…Chauhan et al (17) reported that Foxp3 expression determined the regulatory ability of Treg cells and Foxp3 overexpression could lead to a low immune activity status in the body, which illustrated that Foxp3 was the central regulator of Treg cell activity. Circulating tumor cells (CTCs) are a type of tumor cell that enters the peripheral blood circulation from the primary tumor or metastasis (18). Over the course of a malignancy, tumors may spread from the local site to the blood or lymph circulation.…”

Section: Effect Of Tgf-β1 On Blood Cd4 + Cd25 High Regulatory T Cell mentioning

confidence: 99%

Effect of TGF‑β1 on blood CD4+CD25high regulatory T cell proliferation and Foxp3 expression during non‑small cell lung cancer blood metastasis

Sun

et al. 2018

Exp Ther Med

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Metastatic circulating tumor cells in non-small cell lung cancer (NSCLC) metastasis have been reported to be associated with an immune response. The present study aimed to provide a theoretical basis for the immunomodulatory processes during NSCLC blood metastasis. NSCLC blood and normal peripheral blood mononuclear cells (PBMCs) were collected. The quantity of cluster of differentiation (CD)4CD25 regulatory T (Treg) cells and the intracellular forkhead box protein 3 (Foxp3) expression in CD4CD25 Treg cells were determined by flow cytometry. Furthermore, the effect of transforming growth factor β1 (TGF-β1) on NSCLC blood CD4CD25 Treg cell proliferation was explored by activating blood mononuclear cells with an anti-CD3 monoclonal antibody, interleukin-2 and different doses of TGF-β1. Reverse transcription-quantitative polymerase chain reaction assays were used to detect the mRNA expression of Foxp3. Carboxyfluorescein succinimidyl ester staining was used to analyze the proliferation dynamics of lymphocyte subsets. Results indicate that the proportion of CD4 T cells in the blood of patients with NSCLC was significantly higher compared with normal peripheral blood (P<0.01). Foxp3 expression in NSCLC blood Treg cells was significantly decreased compared with normal peripheral blood (P<0.01). NSCLC blood mononuclear cells treated with TGF-β1 at 1, 5 and 25 ng/ml significantly induced Foxp3 expression in CD4CD25 Treg cells compared with the control group (P<0.05). The proportion of CD4CD25 Treg and CD8 T cells were elevated in generation 6, 7, 8 after 6 days of TGF-β1 treatment compared with untreated cells. The proportion of CD4CD25 Treg and CD8 T cells were elevated in generation 8, 9 and with TGF-β1 treatment after 8 days compared with untreated cells. These results indicate that CD4CD25 Treg cells proliferate at a greater rate compared with CD8 T cells after 4, 6 or 8 days of treatment. The proportion of CD4CD25 Treg cells in NSCLC blood was significantly higher (P<0.05) compared with normal peripheral blood. The number of Foxp3 T cells was significantly lower (P<0.05) compared with normal peripheral blood. The data presented in this study suggest that NSCLC blood CD4CD25 Treg cells are functionally immature and that TGF-β1 may promote maturation.

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Predictive and prognostic value of circulating tumor cell detection in lung cancer: A clinician's perspective

Cited by 32 publications

References 90 publications

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China

Effect of TGF‑β1 on blood CD4+CD25high regulatory T cell proliferation and Foxp3 expression during non‑small cell lung cancer blood metastasis

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