PMID- 36974778
OWN - NLM
STAT- MEDLINE
DCOM- 20230329
LR  - 20230329
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 43
IP  - 4
DP  - 2023 Apr
TI  - Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of 
      Favorable Survival in Patients With Metastatic Breast Cancer.
PG  - 1449-1454
LID - 10.21873/anticanres.16293 [doi]
AB  - 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-DeltaDeltaCT 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.
CI  - Copyright (c) 2023 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Stefanovic, Stefan
AU  - Stefanovic S
AD  - Department of Gynecology and Obstetrics, Mannheim University Hospital, University 
      of Heidelberg, Mannheim, Germany; stefan.stefanovic@umm.de.
FAU - Wirtz, Ralph
AU  - Wirtz R
AD  - Stratifyer Molecular Pathology GmbH, Cologne, Germany.
FAU - Sutterlin, Marc
AU  - Sutterlin M
AD  - Department of Gynecology and Obstetrics, Mannheim University Hospital, University 
      of Heidelberg, Mannheim, Germany.
FAU - Karic, Uros
AU  - Karic U
AD  - Medical Statistics, IMDI Science Center, Belgrade, Serbia.
AD  - Hospital for Infectious and Tropical Diseases, Belgrade University School of 
      Medicine, Belgrade, Serbia.
FAU - Schneeweiss, Andreas
AU  - Schneeweiss A
AD  - National Center for Tumor Diseases, Heidelberg University Hospital, University of 
      Heidelberg, Heidelberg, Germany.
AD  - German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Deutsch, Thomas M
AU  - Deutsch TM
AD  - Department of Gynecology and Obstetrics, Heidelberg University Hospital, 
      University of Heidelberg, Heidelberg, Germany.
FAU - Wallwiener, Markus
AU  - Wallwiener M
AD  - Department of Gynecology and Obstetrics, Heidelberg University Hospital, 
      University of Heidelberg, Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/pathology
MH  - Cohort Studies
MH  - Prospective Studies
MH  - Biomarkers, Tumor/metabolism
MH  - Prognosis
MH  - Histocompatibility Antigens Class I
MH  - HLA-A Antigens
MH  - HLA-B Antigens
MH  - ROC Curve
OTO - NOTNLM
OT  - Breast cancer
OT  - HLA-A
OT  - HLA-B/C
OT  - cut-off
OT  - prognosticator
EDAT- 2023/03/29 06:00
MHDA- 2023/03/29 06:05
CRDT- 2023/03/28 05:33
PHST- 2023/01/18 00:00 [received]
PHST- 2023/02/01 00:00 [revised]
PHST- 2023/02/02 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/03/28 05:33 [entrez]
PHST- 2023/03/29 06:00 [pubmed]
AID - 43/4/1449 [pii]
AID - 10.21873/anticanres.16293 [doi]
PST - ppublish
SO  - Anticancer Res. 2023 Apr;43(4):1449-1454. doi: 10.21873/anticanres.16293.