Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC
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Published:2021-07-13
Issue:
Volume:
Page:
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ISSN:0171-5216
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Container-title:Journal of Cancer Research and Clinical Oncology
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language:en
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Short-container-title:J Cancer Res Clin Oncol
Author:
Zhang Yujuan, Men Yu, Wang Jianyang, Xing Puyuan, Zhao Jun, Li Junling, Xu Danfei, Hui ZhouguangORCID, Cui Wei
Abstract
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.
Funder
National Key R&D Program of China CAMS Innovation Fund for Medical Sciences Clinical Application Project of Beijing Municipal Commission of Science and Technology Beijing Hope Run Special Fund of Cancer Foundation of China CAMS Key lab of translational research on lung cancer
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine
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