Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC
© 2021. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
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| Enthalten in: |
Journal of cancer research and clinical oncology - 148(2022), 5 vom: 18. Mai, Seite 1137-1146 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yujuan [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers, Tumor |
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| Anmerkungen: |
Date Completed 20.04.2022 Date Revised 09.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00432-021-03681-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM328008656 |
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| 245 | 1 | 0 | |a Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC |
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| 500 | |a Date Revised 09.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a OBJECTIVES: To analyze the clinical relevance of heterogeneous phenotypes of peripheral circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: We concluded that E-CTCs with a hybrid E/M phenotype are associated to metastasis in therapy-naïve NSCLC patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a E-CTCs | |
| 650 | 4 | |a E/M-CTCs | |
| 650 | 4 | |a EMT | |
| 650 | 4 | |a Metastasis | |
| 650 | 4 | |a NSCLC | |
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| 700 | 1 | |a Men, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianyang |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Puyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Junling |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Danfei |e verfasserin |4 aut | |
| 700 | 1 | |a Hui, Zhouguang |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Wei |e verfasserin |4 aut | |
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