Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry
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 o...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46458-5 |
| _version_ | 1827590660234936320 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Loukia G. Karacosta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:19:56Z |
| format | Article |
| id | doaj.art-d8612f1f48db4c5a98c79cd070079b2b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:19:56Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d8612f1f48db4c5a98c79cd070079b2b2023-12-10T12:15:26ZengNature PortfolioScientific Reports2045-23222023-12-0113111110.1038/s41598-023-46458-5Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometryLoukia G. Karacosta0Danny Pancirer1Jordan S. Preiss2Jalen A. Benson3Winston Trope4Joseph B. Shrager5Arthur Wai Sung6Joel W. Neal7Sean C. Bendall8Heather Wakelee9Sylvia K. Plevritis10Department of Biomedical Data Science, Stanford UniversityStanford Cancer Institute - Clinical Trials Office, Stanford UniversityStanford Cancer Institute - Clinical Trials Office, Stanford UniversityDepartment of Cardiothoracic Surgery, Stanford UniversityDepartment of Cardiothoracic Surgery, Stanford UniversityDepartment of Cardiothoracic Surgery, Stanford UniversityDivision of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, Stanford UniversityDivision of Oncology, Department of Medicine, Stanford UniversityDepartment of Pathology, Stanford UniversityDivision of Oncology, Department of Medicine, Stanford UniversityDepartment of Biomedical Data Science, Stanford UniversityAbstract 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.https://doi.org/10.1038/s41598-023-46458-5 |
| spellingShingle | 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 Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry Scientific Reports |
| title | Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry |
| title_full | Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry |
| title_fullStr | Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry |
| title_full_unstemmed | Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry |
| title_short | Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry |
| title_sort | phenotyping emt and met cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry |
| url | https://doi.org/10.1038/s41598-023-46458-5 |
| work_keys_str_mv | AT loukiagkaracosta phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT dannypancirer phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT jordanspreiss phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT jalenabenson phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT winstontrope phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT josephbshrager phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT arthurwaisung phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT joelwneal phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT seancbendall phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT heatherwakelee phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry AT sylviakplevritis phenotypingemtandmetcellularstatesinlungcancerpatientliquidbiopsiesatapersonalizedlevelusingmasscytometry |