Cut-off analysis of HLA-A and HLA-B/C expression as a potential prognosticator of favorable survival in patients with metastatic breast cancer
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 t...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 27, 2023
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| In: |
Anticancer research
Year: 2023, Volume: 43, Issue: 4, Pages: 1449-1454 |
| ISSN: | 1791-7530 |
| DOI: | 10.21873/anticanres.16293 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.21873/anticanres.16293 Verlag, lizenzpflichtig, Volltext: https://ar.iiarjournals.org/content/43/4/1449 
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| Author Notes: | Stefan Stefanovic, Ralph Wirtz, Marc Sütterlin, Uros Karic, Andreas Schneeweiss, Thomas M. Deutsch, Markus Wallwiener |
MARC
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| 245 | 1 | 0 | |a Cut-off analysis of HLA-A and HLA-B/C expression as a potential prognosticator of favorable survival in patients with metastatic breast cancer |c Stefan Stefanovic, Ralph Wirtz, Marc Sütterlin, Uros Karic, Andreas Schneeweiss, Thomas M. Deutsch, Markus Wallwiener |
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| 520 | |a 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. | ||
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