Circulating tumor cells as a potential biomarker in diagnosis of lung cancer: a systematic review and meta‐analysis

Huang, Huang; Shi, Yan; Huang, Jietao; Wang, Xiaohui; Zhang, Rui; Chen, Hong

doi:10.1111/crj.12573

Cited by 14 publications

(9 citation statements)

References 34 publications

(60 reference statements)

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“…In NSCLC, CTC analysis is highly demanding due to low CTC-positivity rates compared to other cancers [ 26 , 27 , 28 ]. On the other hand, accumulating evidence supports the clinical relevance of CTC detection in NSCLC [ 26 , 29 , 30 , 31 ]. Moreover, recent reports highlighted the significant heterogeneity of CTCs in patients with lung cancer [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy

Papadaki

Sotiriou

Vasilopoulou

et al. 2020

Cancers

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The current study aimed at the optimization of circulating tumor cell (CTC) enrichment for downstream protein expression analyses in non-small cell lung cancer (NSCLC) to serve as a tool for the investigation of immune checkpoints in real time. Different enrichment approaches—ficoll density, erythrolysis, their combination with magnetic separation, ISET, and Parsortix—were compared in spiking experiments using the A549, H1975, and SKMES-1 NSCLC cell lines. The most efficient methods were tested in patients (n = 15) receiving immunotherapy targeting programmed cell death-1 (PD-1). Samples were immunofluorescently stained for a) cytokeratins (CK)/epithelial cell adhesion molecule (EpCAM)/leukocyte common antigen (CD45), and b) CK/programmed cell death ligand-1 (PD-L1)/ indoleamine-2,3-dioxygenase (IDO). Ficoll, ISET, and Parsortix presented the highest yields and compatibility with phenotypic analysis; however, at the patient level, they provided discordant CTC positivity (13%, 33%, and 60% of patients, respectively) and enriched for distinct CTC populations. IDO and PD-L1 were expressed in 44% and 33% and co-expressed in 19% of CTCs. CTC detection was associated with progressive disease (PD) (p = 0.006), reduced progression-free survival PFS (p = 0.007), and increased risk of relapse (hazard ratio; HR: 10.733; p = 0.026). IDO-positive CTCs were associated with shorter PFS (p = 0.039) and overall survival OS (p = 0.021) and increased risk of death (HR: 5.462; p = 0.039). The current study indicates that CTC analysis according to distinct immune checkpoints is feasible and may provide valuable biomarkers to monitor NSCLC patients treated with anti-PD-1 agents.

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Section: Introductionmentioning

confidence: 99%

Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy

Papadaki

Sotiriou

Vasilopoulou

et al. 2020

Cancers

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“…Circulating tumor cells have been studied as a tumor-dependent biomarker. Despite of an acceptable sensitivity (75%) and specificity (92%) for lung cancer diagnosis (13), and an established role in disease prognosis (14)(15)(16)(17), methods for the detection of circulating tumor cells were still inconsistent and the result interpretation was not standardized (18). Other researchers focused on the host-relative biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Plasma Epstein-Barr Virus-Deoxyribonucleic Acid Copy Number Predicts Disease Progression in Stage I–III Pulmonary Lymphoepithelioma-Like Carcinoma

Qiu

et al. 2020

Front. Oncol.

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Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)-deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC). Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre-and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival. Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52-7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8-99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, p < 0.001). Li et al. EBV-DNA as a Predicting Biomarker Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

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“…However, none have been demonstrated to provide clinical utility 39 , 44 , 45 . CTCs, known as a “liquid biopsy”, have recently emerged as a potential diagnostic biomarker in several cancers, including lung cancer, due to their fine sensitivity and specificity 46 – 48 . The CTC detection might make substantial contributions in the diagnostic workup of indeterminate lung lesions and avoids solid biopsy in selected cases, considering that up to 50% of resected indeterminate lung nodules are benign 49 – 52 .…”

Section: Discussionmentioning

confidence: 99%

Using the New CellCollector to Capture Circulating Tumor Cells from Blood in Different Groups of Pulmonary Disease: A Cohort Study

Shi

et al. 2017

Sci Rep

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Circulating tumor cells (CTCs) are promising biomarkers for clinical application. Cancer screening with Low-Dose Computed Tomography (LDCT) and CTC detections in pulmonary nodule patients has never been reported. The aim of this study was to explore the effectiveness of the combined methods to screen lung cancer. Out of 8313 volunteers screened by LDCT, 32 ground-glass nodules (GGNs) patients and 19 healthy volunteers were randomly selected. Meanwhile, 15 lung cancer patients also enrolled. CellCollector, a new CTC capturing device, was applied for CTCs detection. In GGNs group, five CTC positive patients with six CTCs were identified, 15.6% were positive (range, 1–2). In lung cancer group, 73.3% of the analyzed CellCollector cells were positive (range, 1–7) and no “CTC-like” events were detected in healthy group. All CTCs detected from GGNs group were isolated from the CellCollector functional domain and determined by whole genomic amplification for next-generation sequencing(NGS) analysis. NGS data showed that three cancer-related genes contained mutations in five CTC positive patients, including KIT, SMARCB1 and TP53 genes. In four patients, 16 mutation genes existed. Therefore, LDCT combined with CTC analysis by an in vivo device in high-risk pulmonary nodule patients was a promising way to screen early stage lung cancer.

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Circulating tumor cells as a potential biomarker in diagnosis of lung cancer: a systematic review and meta‐analysis

Abstract: CTCs is a novel potential biomarker in the diagnosis of lung cancer, and more prospective are needed in the future.

Cited by 14 publications

References 34 publications

Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy

Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy

Plasma Epstein-Barr Virus-Deoxyribonucleic Acid Copy Number Predicts Disease Progression in Stage I–III Pulmonary Lymphoepithelioma-Like Carcinoma

Using the New CellCollector to Capture Circulating Tumor Cells from Blood in Different Groups of Pulmonary Disease: A Cohort Study

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