Article ; Online: Diagnosing pleural effusions using mass spectrometry-based multiplexed targeted proteomics quantitating mid- to high-abundance markers of cancer, infection/inflammation and tuberculosis.
2022 Volume 12, Issue 1, Page(s) 3054
Abstract: Pleural effusion (PE) is excess fluid in the pleural cavity that stems from lung cancer, other diseases like extra-pulmonary tuberculosis (TB) and pneumonia, or from a variety of benign conditions. Diagnosing its cause is often a clinical challenge and ... ...
| Abstract | Pleural effusion (PE) is excess fluid in the pleural cavity that stems from lung cancer, other diseases like extra-pulmonary tuberculosis (TB) and pneumonia, or from a variety of benign conditions. Diagnosing its cause is often a clinical challenge and we have applied targeted proteomic methods with the aim of aiding the determination of PE etiology. We developed a mass spectrometry (MS)-based multiple reaction monitoring (MRM)-protein-panel assay to precisely quantitate 53 established cancer-markers, TB-markers, and infection/inflammation-markers currently assessed individually in the clinic, as well as potential biomarkers suggested in the literature for PE classification. Since MS-based proteomic assays are on the cusp of entering clinical use, we assessed the merits of such an approach and this marker panel based on a single-center 209 patient cohort with established etiology. We observed groups of infection/inflammation markers (ADA2, WARS, CXCL10, S100A9, VIM, APCS, LGALS1, CRP, MMP9, and LDHA) that specifically discriminate TB-PEs and other-infectious-PEs, and a number of cancer markers (CDH1, MUC1/CA-15-3, THBS4, MSLN, HPX, SVEP1, SPINT1, CK-18, and CK-8) that discriminate cancerous-PEs. Some previously suggested potential biomarkers did not show any significant difference. Using a Decision Tree/Multiclass classification method, we show a very good discrimination ability for classifying PEs into one of four types: cancerous-PEs (AUC: 0.863), tuberculous-PEs (AUC of 0.859), other-infectious-PEs (AUC of 0.863), and benign-PEs (AUC: 0.842). This type of approach and the indicated markers have the potential to assist in clinical diagnosis in the future, and help with the difficult decision on therapy guidance. |
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| MeSH term(s) | Biomarkers/analysis ; Humans ; Infections/diagnosis ; Infections/metabolism ; Lung Neoplasms/diagnosis ; Lung Neoplasms/metabolism ; Mass Spectrometry/methods ; Pleural Cavity/chemistry ; Pleural Effusion/classification ; Pleural Effusion/diagnosis ; Pleural Effusion/metabolism ; Pneumonia/diagnosis ; Pneumonia/metabolism ; Proteomics/methods ; ROC Curve ; Tuberculosis/diagnosis ; Tuberculosis/metabolism |
| Chemical Substances | Biomarkers |
| Language | English |
| Publishing date | 2022-02-23 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-022-06924-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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