Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer

Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expr...

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Autores principales: Minji Lim, Suhyun Park, Hyoung-Oh Jeong, Sung Hee Park, Sumit Kumar, Aelee Jang, Semin Lee, Dong Uk Kim, Yoon-Kyoung Cho
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:abaf4af3d2cf4497b9755a07958d9f472021-11-11T15:26:47ZCirculating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer10.3390/cancers132152722072-6694https://doaj.org/article/abaf4af3d2cf4497b9755a07958d9f472021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5272https://doaj.org/toc/2072-6694Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expression analysis of single CTCs and CTC clusters in patients with pancreatic cancer and to identify their potential clinical relevance to provide personalized medicine. Epitope-independent, rapid (>3 mL of whole blood/min) isolation of single CTCs and CTC clusters was achieved from a prospective cohort of 16 patients with unresectable pancreatic cancer using a centrifugal microfluidic device. Forty-eight mRNA expressions of individual CTCs and CTC clusters were analyzed to identify pancreatic CTC phenotype. CTC clusters had a larger proportion of mesenchymal expression than single CTCs (<i>p</i> = 0.0004). The presence of CTC clusters positively correlated with poor prognosis (progression-free survival, <i>p</i> = 0.0159; overall survival, <i>p</i> = 0.0186). Furthermore, we found that most CTCs in these patients (90.7%) were cloaked with platelets and found the presence of a positive correlation between the increase in CTC clusters and rapid disease progression during follow-ups. Efficient CTC cluster isolation and analysis techniques will enhance the understanding of complex tumor metastasis processes and can facilitate personalized disease management.Minji LimSuhyun ParkHyoung-Oh JeongSung Hee ParkSumit KumarAelee JangSemin LeeDong Uk KimYoon-Kyoung ChoMDPI AGarticlecirculating tumor cellscirculating tumor cell clusterspancreatic cancerplateletsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5272, p 5272 (2021)
institution DOAJ
collection DOAJ
language EN
topic circulating tumor cells
circulating tumor cell clusters
pancreatic cancer
platelets
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle circulating tumor cells
circulating tumor cell clusters
pancreatic cancer
platelets
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Minji Lim
Suhyun Park
Hyoung-Oh Jeong
Sung Hee Park
Sumit Kumar
Aelee Jang
Semin Lee
Dong Uk Kim
Yoon-Kyoung Cho
Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer
description Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expression analysis of single CTCs and CTC clusters in patients with pancreatic cancer and to identify their potential clinical relevance to provide personalized medicine. Epitope-independent, rapid (>3 mL of whole blood/min) isolation of single CTCs and CTC clusters was achieved from a prospective cohort of 16 patients with unresectable pancreatic cancer using a centrifugal microfluidic device. Forty-eight mRNA expressions of individual CTCs and CTC clusters were analyzed to identify pancreatic CTC phenotype. CTC clusters had a larger proportion of mesenchymal expression than single CTCs (<i>p</i> = 0.0004). The presence of CTC clusters positively correlated with poor prognosis (progression-free survival, <i>p</i> = 0.0159; overall survival, <i>p</i> = 0.0186). Furthermore, we found that most CTCs in these patients (90.7%) were cloaked with platelets and found the presence of a positive correlation between the increase in CTC clusters and rapid disease progression during follow-ups. Efficient CTC cluster isolation and analysis techniques will enhance the understanding of complex tumor metastasis processes and can facilitate personalized disease management.
format article
author Minji Lim
Suhyun Park
Hyoung-Oh Jeong
Sung Hee Park
Sumit Kumar
Aelee Jang
Semin Lee
Dong Uk Kim
Yoon-Kyoung Cho
author_facet Minji Lim
Suhyun Park
Hyoung-Oh Jeong
Sung Hee Park
Sumit Kumar
Aelee Jang
Semin Lee
Dong Uk Kim
Yoon-Kyoung Cho
author_sort Minji Lim
title Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer
title_short Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer
title_full Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer
title_fullStr Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer
title_full_unstemmed Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer
title_sort circulating tumor cell clusters are cloaked with platelets and correlate with poor prognosis in unresectable pancreatic cancer
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/abaf4af3d2cf4497b9755a07958d9f47
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