Cut-off analysis of HLA-A and HLA-B/C expression as a potential prognosticator of favorable survival in patients with metastatic breast cancer

• Verfasst von: Stefanovic, Stefan [VerfasserIn]
• Verfasst von: Wirtz, Ralph [VerfasserIn]
• Verfasst von: Sütterlin, Marc [VerfasserIn]
• Verfasst von: Karic, Uros [VerfasserIn]
• Verfasst von: Schneeweiss, Andreas [VerfasserIn]
• Verfasst von: Deutsch, Thomas M. [VerfasserIn]
• Verfasst von: Wallwiener, Markus [VerfasserIn]
• Titel: Cut-off analysis of HLA-A and HLA-B/C expression as a potential prognosticator of favorable survival in patients with metastatic breast cancer
• Verf.angabe: Stefan Stefanovic, Ralph Wirtz, Marc Sütterlin, Uros Karic, Andreas Schneeweiss, Thomas M. Deutsch, Markus Wallwiener
• E-Jahr: 2023
• Jahr: March 27, 2023
• Umfang: 6 S.
• Fussnoten: Gesehen am 21.06.2023
• Titel Quelle: Enthalten in: Anticancer research
• Ort Quelle: Kapandriti, Attiki, Greece : International Institute of Anticancer Research, 2004
• Jahr Quelle: 2023
• Band/Heft Quelle: 43(2023), 4 vom: März, Seite 1449-1454
• ISSN Quelle: 1791-7530
• DOI: doi:10.21873/anticanres.16293
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Breast cancer
• Sach-SW: cut-off
• Sach-SW: HLA-A
• Sach-SW: HLA-B/C
• Sach-SW: prognosticator
• K10plus-PPN: 185071309X

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.