Department of Gynaecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany.
Institute of Diagnostic Radiology, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany.
Sci Rep. 2020 Sep 25;10(1):15750. doi: 10.1038/s41598-020-72837-3.
The immunosuppressive human leukocyte antigens HLA-G and HLA-F are expressed on trophoblast and malignant cells. Four membrane-bound and three soluble HLA-G protein isoforms have been described, which have different immunosuppressive potentials. HLA-F has three transcript variants, resulting in three different protein isoforms. The aim of this study was to evaluate the prognostic and predictive value of HLA-G and HLA-F protein isoform expression patterns in patients with breast cancer. Core biopsies were taken at diagnosis in patients with HER2+ (n = 28), luminal B-like (n = 49) and triple-negative (n = 38) breast cancers who received neoadjuvant chemotherapy. Expression levels of HLA-F and -G were correlated with the pathological complete response (pCR). Protein expression was determined by Western blot analysis, using two antibodies for each HLA, specific for different isoforms. The protein expression of HLA isoforms did not significantly differ between breast cancer subtypes. However, some initial indications were found for an association between the soluble HLA-G6 protein isoform and pCR in HER2+ breast cancer. The study provides preliminary evidence for the evaluation of HLA-G isoform expression, in particular HLA-G6, as a possible new marker for pCR in HER2+ breast cancer.
免疫抑制性人类白细胞抗原 HLA-G 和 HLA-F 表达于滋养层和恶性细胞上。已经描述了四种膜结合和三种可溶性 HLA-G 蛋白异构体，它们具有不同的免疫抑制潜力。HLA-F 有三个转录变体，导致三个不同的蛋白异构体。本研究旨在评估 HLA-G 和 HLA-F 蛋白异构体表达模式在乳腺癌患者中的预后和预测价值。在接受新辅助化疗的 HER2+（n=28）、腔 B 样（n=49）和三阴性（n=38）乳腺癌患者中，在诊断时进行了核心活检。使用针对不同异构体的两种针对 HLA-F 和 -G 的抗体，通过 Western blot 分析来确定 HLA-F 和 -G 的表达水平与病理完全缓解（pCR）的相关性。在乳腺癌亚型之间，HLA 异构体的蛋白表达没有显著差异。然而，在 HER2+乳腺癌中，发现可溶性 HLA-G6 蛋白异构体与 pCR 之间存在一些初步关联的迹象。该研究为评估 HLA-G 异构体表达，特别是 HLA-G6，作为 HER2+乳腺癌 pCR 的可能新标志物提供了初步证据。
