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Journal of Cancer Research and Clinical Oncology

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01-05-2022 | NSCLC | Original Article – Clinical Oncology

Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC

Authors: Yujuan Zhang, Yu Men, Jianyang Wang, Puyuan Xing, Jun Zhao, Junling Li, Danfei Xu, Zhouguang Hui, Wei Cui

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2022

Abstract

Objectives

To analyze the clinical relevance of heterogeneous phenotypes of peripheral circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC).

Materials and Methods

CTCs in 5 mL venous blood were enriched using the Canpatrol™ CTC technique in 82 NSCLC patients. And then, CTCs were subjected to RNA in situ hybridization with a combination of epithelial (EpCAM and CK8/18/19) and mesenchymal (vimentin and TWIST1) markers.

Results

According to the fluorescent dots, CTCs were classified into three groups, including epithelial CTCs (E-CTC), hybrid epithelial/mesenchymal phenotypes (E/M-CTCs) and mesenchymal CTCs (M-CTCs). In 82 NSCLC cohort, only 2 patients didn’t detect CTCs, the overall CTCs detection rate was 97.5% (80/82). For 60 treatment naïve NSCLC, only one patient didn’t detect CTCs. The median number of total CTCs, hybrid E/M phenotype CTCs, E-CTCs and M-CTCs per 5 mL blood was 22 (range 1–90), 13 (range 0–83), 1 (range 0–17 and 0–47), respectively. Hybrid E/M CTCs, especially the e = m-CTCs, significantly differed between patients with and without distant metastasis. M-CTCs in advanced NSCLC patients were significantly more than the numbers observed in early stage patients. Patients with pure hybrid E/M-CTCs showed a lower proportion in distant metastasis positive cohort compared to negative ones (7% vs 22%), while patients with E + E/M CTCs (20% vs 9%) and E/M + M CTCs (33% vs 20%) showed a higher proportion. CTCs dynamic changes after treatment in 12 advanced NSCLC patients suggested that hybrid E/M-CTCs were related to the primary tumor size at baseline, while M-CTCs may suggest the progression of NSCLC.

Conclusion

We concluded that E-CTCs with a hybrid E/M phenotype are associated to metastasis in therapy-naïve NSCLC patients.

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Title: Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC
Authors: Yujuan Zhang
Yu Men
Jianyang Wang
Puyuan Xing
Jun Zhao
Junling Li
Danfei Xu
Zhouguang Hui
Wei Cui
Publication date: 01-05-2022
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Metastasis
NSCLC
Published in: Journal of Cancer Research and Clinical Oncology / Issue 5/2022
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-021-03681-9

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Abstract

Objectives

Materials and Methods

Results

Conclusion

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