Abstract
Background
Malignant pleural effusion (MPE) is a sign of advanced disease of poor prognosis. As natural killer (NK) cells are involved in the first line of tumour defence, we aimed to validate a new diagnostic and prognostic indicator for MPE based on NK subpopulations of pleural fluid (PF) and peripheral blood (PB).
Methods
NK subpopulations were determined in PF and PB in 71 patients with malignant, paramalignant or benign pleural effusion. The receiver operating characteristic (ROC) curves, Kaplan–Meier, multivariable Cox model and decision trees created with the CHAID (Chi-square automatic interaction detector) methodology were employed.
Results
We demonstrated that the PF/PB ratios of the CD56 bright CD16− and CD56 dim CD16− NK subpopulations were higher (p = 0.013 and p = 0.003, respectively) in MPEs and paramalignant pleural effusions (PPEs) than in benign ones, with an AUC of 0.757 and 0.741, respectively. The PF/PB ratio of CD16+ NK and CD57+ NK obtained a higher hazard ratio (HR) in the crude Cox’s regression analysis. In the adjusted Cox’s regression analysis, the PF/PB ratio of CD16+ NK gave the highest HR (HR 6.1 [1.76–21.1]) (p = 0.004). In the decision tree created for the MPE prognosis, we observed that the main predictor variable among the studied clinical, radiological, and analytical variables was lung mass, and that 92.9% of the patients who survived had a PF/PB ratio of the CD56 dim CD16+ NK subpopulation ≤ 0.43.
Conclusions
Our data suggest that both the PF/PB ratios of cytotoxic subpopulations CD57+ NK and CD16+ NK are useful as a prognostic factor of MPE. Other subpopulations (CD56 bright CD16− and CD56 dim CD16− NK) could help to diagnose MPE.
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Abbreviations
- MPE:
-
Malignant pleural effusion
- NK:
-
Natural killer
- PF:
-
Pleural fluid
- PB:
-
Peripheral blood
- ROC:
-
Receiver operating characteristic
- CHAID:
-
Chi-square automatic interaction detector
- CT:
-
Computed tomography
- PPE:
-
Paramalignant pleural effusion
- CEIC:
-
Committee of Ethics and Clinical Trials
- PBS:
-
Phosphate-buffered saline
- SD:
-
Standard deviation
- AUC:
-
ROC area under the curve
- CI:
-
Confidence intervals
- BPE:
-
Benign pleural effusion
- HR:
-
Hazard ratio
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Acknowledgements
The authors would like to thank the Pulmonology Foundation of the Valencian Community for the grant that this work was awarded with, and with which the monoclonal antibodies employed were obtained. They also thank everyone who collaborated either directly or indirectly in this research.
Funding
Dr. Susana Herrera Lara has received research scholarship support from the Pulmonology Foundation of the Valencian Community.
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SHL designed and conducted the research, collected, analysed and interpreted data, and wrote the manuscript. EF-F designed and conducted the research, interpreted the data, wrote the manuscript and critically revised the article. GJS critically revised the article. JMB analysed and interpreted the data. RAL analysed and interpreted the data. APM provided technical assistance. MMS-V analysed and interpreted the data, performed the statistical analysis and critically revised the article.
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We further confirm that any aspect of the work covered herein that has involved human patients has been conducted with the ethical approval of all the relevant bodies, and that such approvals are acknowledged in the manuscript.
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Herrera Lara, S., Fernández-Fabrellas, E., Juan Samper, G. et al. Cytotoxic Natural Killer Subpopulations as a Prognostic Factor of Malignant Pleural Effusion. Lung 197, 53–60 (2019). https://doi.org/10.1007/s00408-018-0186-7
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DOI: https://doi.org/10.1007/s00408-018-0186-7