Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer

Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), less than 10% of patients survive the first five years when the disease has already spread at primary diagnosis. Methods: Blood samples were taken from 118 NSCLC patients at primary diagnosis or at progression of the dis...

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Autores principales: Eva Obermayr, Nina Koppensteiner, Nicole Heinzl, Eva Schuster, Barbara Holzer, Hannah Fabikan, Christoph Weinlinger, Oliver Illini, Maximilian Hochmair, Robert Zeillinger
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/62a59bcbe60c4ca2b50310a47f3a0116
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spelling oai:doaj.org-article:62a59bcbe60c4ca2b50310a47f3a01162021-11-25T18:08:09ZCancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer10.3390/jpm111112252075-4426https://doaj.org/article/62a59bcbe60c4ca2b50310a47f3a01162021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1225https://doaj.org/toc/2075-4426Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), less than 10% of patients survive the first five years when the disease has already spread at primary diagnosis. Methods: Blood samples were taken from 118 NSCLC patients at primary diagnosis or at progression of the disease before the start of a new treatment line and enriched for circulating tumor cells (CTCs) by microfluidic Parsortix™ (Angle plc, Guildford GU2 7AF, UK) technology. The gene expression of epithelial cancer stem cell (CSC), epithelial to mesenchymal (EMT), and lung-related markers was assessed by qPCR, and the association of each marker with overall survival (OS) was evaluated using log-rank tests. Results: EpCAM was the most prevalent transcript, with 53.7% positive samples at primary diagnosis and 25.6% at recurrence. EpCAM and CK19, as well as NANOG, PROM1, TERT, CDH5, FAM83A, and PTHLH transcripts, were associated with worse OS. However, only the CSC-specific NANOG and PROM1 were related to the outcome both at primary diagnosis (NANOG: HR 3.21, 95%CI 1.02–10.14, <i>p</i> = 0.016; PROM1: HR 4.23, 95% CI 0.65–27.56, <i>p</i> = 0.007) and disease progression (NANOG: HR 4.17, 95%CI 0.72–24.14, <i>p</i> = 0.025; PROM1: HR 4.77, 95% CI 0.29–78.94, <i>p</i> = 0.032). Conclusions: The present study further underlines the relevance of the molecular characterization of CTCs. Our multi-marker analysis highlighted the prognostic value of cancer stem cell-related transcripts at primary diagnosis and disease progression.Eva ObermayrNina KoppensteinerNicole HeinzlEva SchusterBarbara HolzerHannah FabikanChristoph WeinlingerOliver IlliniMaximilian HochmairRobert ZeillingerMDPI AGarticlenon-small cell lung cancercirculating tumor cellscancer stem cellmicrofluidicsgene expression analysisMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1225, p 1225 (2021)
institution DOAJ
collection DOAJ
language EN
topic non-small cell lung cancer
circulating tumor cells
cancer stem cell
microfluidics
gene expression analysis
Medicine
R
spellingShingle non-small cell lung cancer
circulating tumor cells
cancer stem cell
microfluidics
gene expression analysis
Medicine
R
Eva Obermayr
Nina Koppensteiner
Nicole Heinzl
Eva Schuster
Barbara Holzer
Hannah Fabikan
Christoph Weinlinger
Oliver Illini
Maximilian Hochmair
Robert Zeillinger
Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
description Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), less than 10% of patients survive the first five years when the disease has already spread at primary diagnosis. Methods: Blood samples were taken from 118 NSCLC patients at primary diagnosis or at progression of the disease before the start of a new treatment line and enriched for circulating tumor cells (CTCs) by microfluidic Parsortix™ (Angle plc, Guildford GU2 7AF, UK) technology. The gene expression of epithelial cancer stem cell (CSC), epithelial to mesenchymal (EMT), and lung-related markers was assessed by qPCR, and the association of each marker with overall survival (OS) was evaluated using log-rank tests. Results: EpCAM was the most prevalent transcript, with 53.7% positive samples at primary diagnosis and 25.6% at recurrence. EpCAM and CK19, as well as NANOG, PROM1, TERT, CDH5, FAM83A, and PTHLH transcripts, were associated with worse OS. However, only the CSC-specific NANOG and PROM1 were related to the outcome both at primary diagnosis (NANOG: HR 3.21, 95%CI 1.02–10.14, <i>p</i> = 0.016; PROM1: HR 4.23, 95% CI 0.65–27.56, <i>p</i> = 0.007) and disease progression (NANOG: HR 4.17, 95%CI 0.72–24.14, <i>p</i> = 0.025; PROM1: HR 4.77, 95% CI 0.29–78.94, <i>p</i> = 0.032). Conclusions: The present study further underlines the relevance of the molecular characterization of CTCs. Our multi-marker analysis highlighted the prognostic value of cancer stem cell-related transcripts at primary diagnosis and disease progression.
format article
author Eva Obermayr
Nina Koppensteiner
Nicole Heinzl
Eva Schuster
Barbara Holzer
Hannah Fabikan
Christoph Weinlinger
Oliver Illini
Maximilian Hochmair
Robert Zeillinger
author_facet Eva Obermayr
Nina Koppensteiner
Nicole Heinzl
Eva Schuster
Barbara Holzer
Hannah Fabikan
Christoph Weinlinger
Oliver Illini
Maximilian Hochmair
Robert Zeillinger
author_sort Eva Obermayr
title Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
title_short Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
title_full Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
title_fullStr Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
title_full_unstemmed Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer
title_sort cancer stem cell-like circulating tumor cells are prognostic in non-small cell lung cancer
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/62a59bcbe60c4ca2b50310a47f3a0116
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