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Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer

Circulating tumor microemboli (CTM) aggregated by ≥ 2 circulating tumor cells (CTCs) are more migratory than single CTCs. Aside from the plasticity in their molecular characteristics, which have been considered tumor migration, CTM also possesses high size heterogeneity. This study, therefore, syste...

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Autores principales: Chen, Yang, Yuan, Jiajia, Li, Yanyan, Li, Xue, Yang, Ying, Li, Jian, Li, Yilin, Shen, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338835/
https://www.ncbi.nlm.nih.gov/pubmed/34152566
http://dx.doi.org/10.1007/s13577-021-00568-2
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author Chen, Yang
Yuan, Jiajia
Li, Yanyan
Li, Xue
Yang, Ying
Li, Jian
Li, Yilin
Shen, Lin
author_facet Chen, Yang
Yuan, Jiajia
Li, Yanyan
Li, Xue
Yang, Ying
Li, Jian
Li, Yilin
Shen, Lin
author_sort Chen, Yang
collection PubMed
description Circulating tumor microemboli (CTM) aggregated by ≥ 2 circulating tumor cells (CTCs) are more migratory than single CTCs. Aside from the plasticity in their molecular characteristics, which have been considered tumor migration, CTM also possesses high size heterogeneity. This study, therefore, systematically investigated the heterogeneous sizes of CTM and their involvement in therapeutic resistance in 114 patients with advanced gastric cancer (GC) using a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. CTM, which was pre-therapeutically detected in 33.3% of GC patients, can further form in another 34.78% of patients following chemo-/targeted therapies. The presence of CTM is relevant to liver metastasis as well as higher CTC levels (≥ 5/6 mL). Further size-based profiling of GC-CTM revealed that CTM with 2 CTCs (CTM(2)) was the dominant subtype, accounting for 50.0% of all detected GC-CTMs. However, CTM with 3–4 CTCs (CTM(3–4)) specifically associates with chemo-/targeted therapeutic resistance and inferior prognosis. Patients with ≥ 1 CTM(3–4)/6 mL have shorter median progression-free survival and median overall survival. Unlike CTM(2) and CTM(3–4), which are detectable in pre-therapy and post-therapy, larger aggregated CTM(≥5) (CTM with ≥ 5 CTCs) was only intra-therapeutically detected in four HER2(+) GC patients, of which three experienced liver metastases. Obtained results suggested that the cluster size of GC-CTM should be dynamically profiled beyond pre-therapeutic whole CTM enumeration in terms of chemo-/targeted resistance or metastasis monitoring. GC-CTM(3–4) could be a potential indicator of therapeutic resistance, while the dynamic presence of GC-CTM(≥5) implies liver metastasis in HER2(+) GC patients.
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spelling pubmed-83388352021-08-20 Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer Chen, Yang Yuan, Jiajia Li, Yanyan Li, Xue Yang, Ying Li, Jian Li, Yilin Shen, Lin Hum Cell Research Article Circulating tumor microemboli (CTM) aggregated by ≥ 2 circulating tumor cells (CTCs) are more migratory than single CTCs. Aside from the plasticity in their molecular characteristics, which have been considered tumor migration, CTM also possesses high size heterogeneity. This study, therefore, systematically investigated the heterogeneous sizes of CTM and their involvement in therapeutic resistance in 114 patients with advanced gastric cancer (GC) using a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. CTM, which was pre-therapeutically detected in 33.3% of GC patients, can further form in another 34.78% of patients following chemo-/targeted therapies. The presence of CTM is relevant to liver metastasis as well as higher CTC levels (≥ 5/6 mL). Further size-based profiling of GC-CTM revealed that CTM with 2 CTCs (CTM(2)) was the dominant subtype, accounting for 50.0% of all detected GC-CTMs. However, CTM with 3–4 CTCs (CTM(3–4)) specifically associates with chemo-/targeted therapeutic resistance and inferior prognosis. Patients with ≥ 1 CTM(3–4)/6 mL have shorter median progression-free survival and median overall survival. Unlike CTM(2) and CTM(3–4), which are detectable in pre-therapy and post-therapy, larger aggregated CTM(≥5) (CTM with ≥ 5 CTCs) was only intra-therapeutically detected in four HER2(+) GC patients, of which three experienced liver metastases. Obtained results suggested that the cluster size of GC-CTM should be dynamically profiled beyond pre-therapeutic whole CTM enumeration in terms of chemo-/targeted resistance or metastasis monitoring. GC-CTM(3–4) could be a potential indicator of therapeutic resistance, while the dynamic presence of GC-CTM(≥5) implies liver metastasis in HER2(+) GC patients. Springer Singapore 2021-06-21 2021 /pmc/articles/PMC8338835/ /pubmed/34152566 http://dx.doi.org/10.1007/s13577-021-00568-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Chen, Yang
Yuan, Jiajia
Li, Yanyan
Li, Xue
Yang, Ying
Li, Jian
Li, Yilin
Shen, Lin
Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
title Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
title_full Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
title_fullStr Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
title_full_unstemmed Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
title_short Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
title_sort profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338835/
https://www.ncbi.nlm.nih.gov/pubmed/34152566
http://dx.doi.org/10.1007/s13577-021-00568-2
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