Phenotyping EMT and Met Cellular States in Lung Cancer Patient Liquid Biopsies at a Personalized Level Using Mass Cytometry

Authors

Loukia G Karacosta
Danny Pancirer
Jordan S Preiss
Jalen A Benson
Winston Trope
Joseph B Shrager
Arthur Wai Sung
Joel W Neal
Sean C Bendall
Heather Wakelee
Sylvia K Plevritis

Publication Date

12-8-2023

Journal

Scientific Reports

DOI

10.1038/s41598-023-46458-5

PMID

38065965

PMCID

PMC10709404

PubMedCentral® Posted Date

December 2023

PubMedCentral® Full Text Version

Post-print

Abstract

Malignant pleural effusions (MPEs) can be utilized as liquid biopsy for phenotyping malignant cells and for precision immunotherapy, yet MPEs are inadequately studied at the single-cell proteomic level. Here we leverage mass cytometry to interrogate immune and epithelial cellular profiles of primary tumors and pleural effusions (PEs) from early and late-stage non-small cell lung cancer (NSCLC) patients, with the goal of assessing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in patient specimens. By using the EMT-MET reference map PHENOSTAMP, we observe a variety of EMT states in cytokeratin positive (CK+) cells, and report for the first time MET-enriched CK+ cells in MPEs. We show that these states may be relevant to disease stage and therapy response. Furthermore, we found that the fraction of CD33+ myeloid cells in PEs was positively correlated to the fraction of CK+ cells. Longitudinal analysis of MPEs drawn 2 months apart from a patient undergoing therapy, revealed that CK+ cells acquired heterogeneous EMT features during treatment. We present this work as a feasibility study that justifies deeper characterization of EMT and MET states in malignant cells found in PEs as a promising clinical platform to better evaluate disease progression and treatment response at a personalized level.

Keywords

Humans, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Proteomics, Epithelial-Mesenchymal Transition, Pleural Effusion, Malignant, Pleural Effusion, Liquid Biopsy

Published Open-Access

yes

Recommended Citation

Karacosta, Loukia G; Pancirer, Danny; Preiss, Jordan S; et al., "Phenotyping EMT and Met Cellular States in Lung Cancer Patient Liquid Biopsies at a Personalized Level Using Mass Cytometry" (2023). Faculty, Staff and Student Publications. 1277.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/1277