Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC
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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E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
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Enthalten in: |
Journal of cancer research and clinical oncology - 148(2021), 5 vom: 13. Juli, Seite 1137-1146 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhang, Yujuan [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Anmerkungen: |
© The Author(s) 2021 |
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doi: |
10.1007/s00432-021-03681-9 |
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funding: |
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PPN (Katalog-ID): |
OLC2130182453 |
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520 | |a 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. | ||
650 | 4 | |a NSCLC | |
650 | 4 | |a E-CTCs | |
650 | 4 | |a E/M-CTCs | |
650 | 4 | |a EMT | |
650 | 4 | |a Metastasis | |
700 | 1 | |a Men, Yu |4 aut | |
700 | 1 | |a Wang, Jianyang |4 aut | |
700 | 1 | |a Xing, Puyuan |4 aut | |
700 | 1 | |a Zhao, Jun |4 aut | |
700 | 1 | |a Li, Junling |4 aut | |
700 | 1 | |a Xu, Danfei |4 aut | |
700 | 1 | |a Hui, Zhouguang |0 (orcid)0000-0002-7189-4692 |4 aut | |
700 | 1 | |a Cui, Wei |4 aut | |
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