Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry

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

doi:10.1038/s41598-023-46458-5

Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry

Sci Rep. 2023 Dec 8;13(1):21781. doi: 10.1038/s41598-023-46458-5.

Authors

Loukia G Karacosta^{1

2}, Danny Pancirer³, Jordan S Preiss³, Jalen A Benson⁴, Winston Trope⁴, Joseph B Shrager^{4

5}, Arthur Wai Sung⁶, Joel W Neal⁷, Sean C Bendall⁸, Heather Wakelee⁷, Sylvia K Plevritis^{9

10}

Affiliations

¹ Department of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA.
² Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
³ Stanford Cancer Institute - Clinical Trials Office, Stanford University, Stanford, CA, 94305, USA.
⁴ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, 94305, USA.
⁵ Palo Alto VA Health Care System, Palo Alto, USA.
⁶ Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
⁷ Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
⁸ Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
⁹ Department of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA. sylvia.plevritis@stanford.edu.
¹⁰ Department of Radiology, Stanford University, Stanford, CA, 94305, USA. sylvia.plevritis@stanford.edu.

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.

MeSH terms

Carcinoma, Non-Small-Cell Lung* / pathology
Epithelial-Mesenchymal Transition / physiology
Humans
Liquid Biopsy
Lung Neoplasms* / pathology
Pleural Effusion*
Pleural Effusion, Malignant* / drug therapy
Proteomics

Grants and funding

R25 CA180993/CA/NCI NIH HHS/United States