A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups

Lindsay, Colin R.; Faugeroux, Vincent; Michiels, Stefan; Pailler, Emma; Facchinetti, Fabio; Ou, Dan; Bluthgen, M.V.; Pannet, Chloe; Ngo-Camus, Maud; Bescher, G.; Caramella, Caroline; Billiot, Fanny; Remón, Jordi; Planchard, David; Soria, Jean Charles; Besse, Benjamin; Farace, Françoise

doi:10.1093/annonc/mdx156

Cited by 82 publications

(100 citation statements)

References 26 publications

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“…In total, 89.6% of the GC patients had detectable CTCs, and 54.4% of these patients had greater than 4 CTCs/7.5 mL. These levels are significantly higher than those observed with other tumor types, perhaps reflecting the high affinity for blood vessels exhibited by trophoblastic cells and the tendency of GC to metastasize through the hematogenous route . The number of CTCs is closely associated with the primary tumor size and the number of metastases, consistent with findings in non‐small‐cell lung cancer and breast cancer .…”

Section: Discussionsupporting

confidence: 79%

Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma

Hou

Zhang

et al. 2018

Intl Journal of Cancer

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Gestational choriocarcinoma (GC) is a highly aggressive tumor. In our study, we systematically investigated EpCAM/CD147 expression characteristics in patients with GC and assessed the role of circulating tumor cells (CTCs) in predicting chemotherapy response and disease progression. GC tissues were positive for either epithelial cellular adhesion molecule (EpCAM) or CD147, and all samples exhibited strong human chorionic gonadotropin (HCG) expression. Among all the recruited patients (n = 115), 103 had at least 1 CTC in a 7.5-mL peripheral blood sample, and the percentage of patients with ≥4 CTCs in a particular FIGO stage group increased with a higher FIGO stage (p < 0.001). Furthermore, the pretreatment CTC count was related to tumor size (r = 0.225, p = 0.015) and the number of metastases (r = 0.603, p < 0.001). A progression analysis showed that among the 115 included patients who qualified for further examination, 52 of the 64 patients defined as progressive had ≥4 pretreatment CTCs, while only 7 of the 51 non-progressive patients had ≥4 pretreatment CTCs (p < 0.001). In multivariate analysis, CTCs (≥4) remained the strongest predictor of PFS when other prognostic markers, FIGO score and FIGO stage were included. Moreover, based on the chemotherapy response, patients with ≥4 CTCs were more likely to be resistant to chemotherapy than those with <4 CTCs (P < 0.001). These findings demonstrates the feasibility of CTC detection in cases of GC by adopting EpCAM/CD147 antibodies together as capturing antibodies. The CTC count is a promising indicator in the evaluation of biological activities and the chemotherapy response in GC patients.

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Section: Discussionsupporting

confidence: 79%

Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma

Hou

Zhang

et al. 2018

Intl Journal of Cancer

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“…In the Lindsay's et al current study (10), the authors also correlated the total CTC number as well as the vim+ subgroup with the presence of EGFR, ALK and KRAS mutations. Of the patients tested for genetic aberration, 24.4% were KRAS mutated, 22.3% were EGFR mutated, and 14.4% ALK rearranged.…”

Section: Editorialmentioning

confidence: 78%

“…One of the hallmarks of EMT in tumor cells is the progressively loss of epithelial antigens, including EpCAM and cytokeratins (14), while developing mesenchymal markers, such as vimentin (15). In order to overcome this limitation in the present study, Lindsay et al took advantage of the free channel of the CellSearch platform and added a FITC-labelled anti-vimentin antibody aiming to further characterize patients' CTCs according to their vimentin expression during treatment; a patient was considered as CTC-positive if at least one vim+ cell was detected (10). Twenty-four (19.2%) patients had ≥5 CTCs/10 mL of blood and 5.6% of them were vim+.…”

Section: Editorialmentioning

confidence: 99%

Association of epithelial-to-mesenchymal transition circulating tumor cells in non-small cell lung cancer (NSCLC) molecular subgroups

Messaritakis¹,

Κotsakis²,

Georgoulias³

2017

J. Thorac. Dis.

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“…showed the prognostic value of CTCs counted by the CellSearch system in patients with treatment-naïve stage IIIb/IV NSCLC. 49 Punnoose et al 50 reported that higher baseline CTC counts were associated with response to treatment and decreased CTC counts following treatment were associated with longer progression-free survival. The prognostic and predictive value of CTCs counted by our system will be evaluated in future clinical studies with optimization of timing of blood collection.…”

Section: Discussionmentioning

confidence: 99%

Isolation and molecular analysis of circulating tumor cells from lung cancer patients using a microfluidic chip type cell sorter

Watanabe

Kenmotsu

et al. 2018

Cancer Science

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Circulating tumor cells (CTCs) are a tumor‐derived material utilized for liquid‐based biopsy; however, capturing rare CTCs for further molecular analysis remains technically challenging, especially in non‐small‐cell lung cancer. Here, we report the results of a clinical evaluation of On‐chip Sort, a disposable microfluidic chip‐based cell sorter, for capture and molecular analysis of CTCs from patients with lung adenocarcinoma. Peripheral blood was collected from 30 metastatic lung adenocarcinoma patients to enumerate CTCs using both On‐chip Sort and CellSearch in a blind manner. Captured cells by On‐chip Sort were subjected to further molecular analysis. Peripheral blood samples were also used for detection of EGFR mutations in plasma using droplet digital PCR. Significantly more CTCs were detected by On‐chip Sort (22/30; median 5; range, 0–18 cells/5 mL blood) than by CellSearch (9/30; median, 0; range, 0–12 cells/7.5 mL) (P < 0.01). Thirteen of 30 patients who had a negative CTC count by CellSearch had a positive CTC count by On‐chip Sort. EGFR mutations in CTCs captured by On‐chip Sort were observed in 40.0% (8/20) of patients with EGFR‐mutated primary tumor. EGFR mutations were often observed in 53.3% (8/15) of patients detected in plasma DNA. Expressions of EGFR and vimentin protein on CTCs were also successfully assessed using On‐chip Sort. These results suggest that On‐chip Sort is an efficient method to detect and capture rare CTCs from patients with lung adenocarcinoma that are undetectable with CellSearch. Mutation detection using isolated CTCs remains to be further tackled (UMIN000012488).

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A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups

Abstract: We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma.

Cited by 82 publications

References 26 publications

Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma

Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma

Association of epithelial-to-mesenchymal transition circulating tumor cells in non-small cell lung cancer (NSCLC) molecular subgroups

Isolation and molecular analysis of circulating tumor cells from lung cancer patients using a microfluidic chip type cell sorter

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