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Discrimination of Head and Neck Squamous Cell Carcinoma Patients and Healthy Adults by 10-Color Flow Cytometry: Development of a Score Based on Leukocyte Subsets

1
Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Liebigstr. 10-14, 04103 Leipzig, Germany
2
LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany
3
Clinical Trial Centre Leipzig, University Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany
4
Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Härtelstr. 10-18, 04107 Leipzig, Germany
5
Department of Precision Instruments, Tsinghua University, Beijing 100084, China
6
Fraunhofer Institute for Cell Therapy and Immunology IZI, Perlickstr. 1, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
These authors share equal contribution.
These authors share equal senior authorship.
Cancers 2019, 11(6), 814; https://doi.org/10.3390/cancers11060814
Received: 22 March 2019 / Revised: 29 May 2019 / Accepted: 10 June 2019 / Published: 12 June 2019
(This article belongs to the Special Issue New Biomarkers in Cancers)
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Abstract

Background: Leukocytes in peripheral blood (PB) are prognostic biomarkers in head and neck squamous cell carcinoma cancer patients (HNSCC-CPs), but differences between HNSCC-CPs and healthy adults (HAs) are insufficiently described. Methods: 10-color flow cytometry (FCM) was used for in-depth immunophenotyping of PB samples of 963 HAs and 101 therapy-naïve HNSCC-CPs. Absolute (AbsCC) and relative cell counts (RelCC) of leukocyte subsets were determined. A training cohort (TC) of 43 HNSCC-CPs and 43 HAs, propensity score (PS)-matched according to age, sex, alcohol, and smoking, was used to develop a score consecutively approved in a validation cohort (VC). Results: Differences in AbsCC were detected in leukocyte subsets (p < 0.001), but had low power in discriminating HNSCC-CPs and HAs. Consequently, RelCC of nine leukocyte subsets in the TC were used to calculate 36 ratios; receiver operating characteristic (ROC) curves defined optimum cut-off values. Binary classified data were combined in a score based on four ratios: monocytes-to-granulocytes (MGR), classical monocytes-to-monocytes (clMMR), monocytes-to-lymphocytes (MLR), and monocytes-to-T-lymphocytes (MTLR); ≥3 points accurately discriminate HNSCC-CPs and HAs in the PS-matched TC (p = 2.97 × 10−17), the VC (p = 4.404 × 10−178), and both combined (p = 7.74 × 10−199). Conclusions: RelCC of leukocyte subsets in PB of HNSCC-CPs differ significantly from those of HAs. A score based on MGR, clMMR, MLR, and MTLR allows for accurate discrimination. View Full-Text
Keywords: head and neck squamous cell carcinoma (HNSCC); multicolor flow cytometry; peripheral blood; leukocyte subsets; cancer biomarker; predictive value; monocytes-to-lymphocytes ratio (MLR); monocytes-to-granulocytes ratio (MGR); classical monocytes; propensity score matching head and neck squamous cell carcinoma (HNSCC); multicolor flow cytometry; peripheral blood; leukocyte subsets; cancer biomarker; predictive value; monocytes-to-lymphocytes ratio (MLR); monocytes-to-granulocytes ratio (MGR); classical monocytes; propensity score matching
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Wichmann, G.; Gaede, C.; Melzer, S.; Bocsi, J.; Henger, S.; Engel, C.; Wirkner, K.; Wenning, J.R.; Wald, T.; Freitag, J.; Willner, M.; Kolb, M.; Wiegand, S.; Löffler, M.; Dietz, A.; Tárnok, A. Discrimination of Head and Neck Squamous Cell Carcinoma Patients and Healthy Adults by 10-Color Flow Cytometry: Development of a Score Based on Leukocyte Subsets. Cancers 2019, 11, 814.

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