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Research ArticleExperimental Studies

Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of Favorable Survival in Patients With Metastatic Breast Cancer

STEFAN STEFANOVIC, RALPH WIRTZ, MARC SÜTTERLIN, UROS KARIC, ANDREAS SCHNEEWEISS, THOMAS M. DEUTSCH and MARKUS WALLWIENER
Anticancer Research April 2023, 43 (4) 1449-1454; DOI: https://doi.org/10.21873/anticanres.16293
STEFAN STEFANOVIC
1Department of Gynecology and Obstetrics, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany;
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  • For correspondence: stefan.stefanovic@umm.de
RALPH WIRTZ
2Stratifyer Molecular Pathology GmbH, Cologne, Germany;
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MARC SÜTTERLIN
1Department of Gynecology and Obstetrics, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany;
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UROS KARIC
3Medical Statistics, IMDI Science Center, Belgrade, Serbia;
4Hospital for Infectious and Tropical Diseases, Belgrade University School of Medicine, Belgrade, Serbia;
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ANDREAS SCHNEEWEISS
5National Center for Tumor Diseases, Heidelberg University Hospital, University of Heidelberg, Heidelberg, Germany;
6German Cancer Research Center (DKFZ), Heidelberg, Germany;
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THOMAS M. DEUTSCH
7Department of Gynecology and Obstetrics, Heidelberg University Hospital, University of Heidelberg, Heidelberg, Germany
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MARKUS WALLWIENER
7Department of Gynecology and Obstetrics, Heidelberg University Hospital, University of Heidelberg, Heidelberg, Germany
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Abstract

Background/Aim: Loss of differentiation of breast cancer cells in association with a down-regulated class I human leukocyte antigen (HLA) expression can lead to proliferation unhampered by cytotoxic T lymphocytes, which has been proven to be of prognostic relevance. The objective of this study was to determine the levels of HLA-A and HLA-B/C expression in metastatic breast cancer (MBC) cells and their usefulness for predicting 5-year survival. Materials and Methods: This prospective double-blinded cohort study analyzed patients starting a new line of therapy for MBC. RT-qPCR was used to determine the levels of HLA-A and B/C expression in MBC cells and the mRNA-based tumor intrinsic subtype. Two receiver operating characteristic curves (ROC) were constructed in order to determine whether HLA-A and HLA-B/C expression levels can be used for predicting 5-year survival. Youden J points, and sensitivity and specificity optimized cut-off points were determined for both ROC curves. Results: We enrolled 34 patients. The ROC curve for HLA-B/C had the highest AUC compared to HLA-A (0.55 vs. 0.42). High levels of HLA-A and HLA-B/C expression (40-ΔΔCT of 33.5 and 31.9, respectively) were highly specific (reaching 87.5% for HLA-A and even 100% specificity for HLA-B/C) yet insensitive for five-year survival in our study. Conclusion: High expression of certain class I HLA molecule subtypes by MBCs, in particular high HLA-A or B/C expression by MBC cells seems very specific in predicting the 5-year survival. We determined cut-off values for these HLA molecule clusters with high specificity, which might help identify patients with a favorable prognosis as prognosticators of a 5-year overall survival if their sensitivity is improved in larger prospective cohorts.

Key Words:
  • Breast cancer
  • HLA-A
  • HLA-B/C
  • cut-off
  • prognosticator
  • Received January 18, 2023.
  • Revision received February 1, 2023.
  • Accepted February 2, 2023.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 43 (4)
Anticancer Research
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April 2023
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Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of Favorable Survival in Patients With Metastatic Breast Cancer
STEFAN STEFANOVIC, RALPH WIRTZ, MARC SÜTTERLIN, UROS KARIC, ANDREAS SCHNEEWEISS, THOMAS M. DEUTSCH, MARKUS WALLWIENER
Anticancer Research Apr 2023, 43 (4) 1449-1454; DOI: 10.21873/anticanres.16293

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Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of Favorable Survival in Patients With Metastatic Breast Cancer
STEFAN STEFANOVIC, RALPH WIRTZ, MARC SÜTTERLIN, UROS KARIC, ANDREAS SCHNEEWEISS, THOMAS M. DEUTSCH, MARKUS WALLWIENER
Anticancer Research Apr 2023, 43 (4) 1449-1454; DOI: 10.21873/anticanres.16293
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Keywords

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