Characterizing epithelial-mesenchymal transition-linked heterogeneity in breast cancer circulating tumor cells at a single-cell level

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F25%3A00080414" target="_blank" >RIV/00209805:_____/25:00080414 - isvavai.cz</a>

Výsledek na webu

<a href="https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1878-0261.70132" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1878-0261.70132</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/1878-0261.70132" target="_blank" >10.1002/1878-0261.70132</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Characterizing epithelial-mesenchymal transition-linked heterogeneity in breast cancer circulating tumor cells at a single-cell level

Popis výsledku v původním jazyce

Epithelial-mesenchymal transition (EMT) generates heterogeneity in circulating tumor cells (CTCs), affecting their biological properties and hampering their detection. This limits our understanding of the mechanisms underlying hematogenous dissemination, especially in early breast cancer (BC), where CTCs are rare. Here, we aimed to detect CTCs with different EMT statuses from BC patients. CTCs in blood samples from 107 BC patients were evaluated using immunomagnetic depletion and multi-marker immunofluorescence (EpCAM, E-cadherin, MCAM, cell surface vimentin, CD31, CD45), followed by single-cell transcriptomics. CTCs were detected in 51.9% of therapy-naïve early BC cases, with 3.8% showing only epithelial CTCs (eCTCs), 5.8% epithelial-mesenchymal (emCTCs), 26.0% mesenchymal (mCTCs), and 16.3% mixed phenotypes. CTC heterogeneity was more frequent in triple-negative (86%) than in luminal BC (17%, P = 0.008). Lymph node involvement strongly predicted dissemination of all CTC phenotypes, while tumor size correlated with mCTC abundance. Single-cell RNA sequencing revealed downregulation of ribosomal genes and translation inhibition in CTCs with mesenchymal features, linked to mTORC1 signaling. Findings were also validated in an independent dataset, highlighting vulnerabilities in CTCs during dissemination.

Název v anglickém jazyce

Characterizing epithelial-mesenchymal transition-linked heterogeneity in breast cancer circulating tumor cells at a single-cell level

Popis výsledku anglicky

Epithelial-mesenchymal transition (EMT) generates heterogeneity in circulating tumor cells (CTCs), affecting their biological properties and hampering their detection. This limits our understanding of the mechanisms underlying hematogenous dissemination, especially in early breast cancer (BC), where CTCs are rare. Here, we aimed to detect CTCs with different EMT statuses from BC patients. CTCs in blood samples from 107 BC patients were evaluated using immunomagnetic depletion and multi-marker immunofluorescence (EpCAM, E-cadherin, MCAM, cell surface vimentin, CD31, CD45), followed by single-cell transcriptomics. CTCs were detected in 51.9% of therapy-naïve early BC cases, with 3.8% showing only epithelial CTCs (eCTCs), 5.8% epithelial-mesenchymal (emCTCs), 26.0% mesenchymal (mCTCs), and 16.3% mixed phenotypes. CTC heterogeneity was more frequent in triple-negative (86%) than in luminal BC (17%, P = 0.008). Lymph node involvement strongly predicted dissemination of all CTC phenotypes, while tumor size correlated with mCTC abundance. Single-cell RNA sequencing revealed downregulation of ribosomal genes and translation inhibition in CTCs with mesenchymal features, linked to mTORC1 signaling. Findings were also validated in an independent dataset, highlighting vulnerabilities in CTCs during dissemination.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular oncology

ISSN

1574-7891

e-ISSN

1878-0261

Svazek periodika

19

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

3685-3705

Kód UT WoS článku

001586477300001

EID výsledku v databázi Scopus

2-s2.0-105018329889