Department of Gynecology and Obstetrics, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany;
Stratifyer Molecular Pathology GmbH, Cologne, Germany.
Anticancer Res. 2023 Apr;43(4):1449-1454. doi: 10.21873/anticanres.16293.
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.
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.
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.
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.
背景/目的：乳腺癌细胞分化的丧失与 HLA Ⅰ类分子表达下调相关，这会导致细胞不受细胞毒性 T 淋巴细胞的限制而增殖，而这已被证明与预后相关。本研究的目的是确定转移性乳腺癌（MBC）细胞中 HLA-A 和 HLA-B/C 的表达水平及其对预测 5 年生存率的用途。
这项前瞻性、双盲队列研究分析了开始接受新的 MBC 治疗方案的患者。实时定量 RT-PCR 用于确定 MBC 细胞中 HLA-A 和 B/C 的表达水平以及基于 mRNA 的肿瘤内在亚型。构建了两条 ROC 曲线，以确定 HLA-A 和 HLA-B/C 的表达水平是否可用于预测 5 年生存率。确定了两条 ROC 曲线的约登指数、敏感性和特异性最佳截断点。
我们共纳入了 34 例患者。与 HLA-A 相比，HLA-B/C 的 ROC 曲线具有更高的 AUC（0.55 比 0.42）。在我们的研究中，HLA-A 和 HLA-B/C 高表达（分别为 40-ΔΔCT 值为 33.5 和 31.9）具有高度特异性（HLA-A 特异性达到 87.5%，甚至 HLA-B/C 的特异性达到 100%），但对 5 年生存率的敏感性较低。
MBC 中某些 HLA Ⅰ类分子亚型的高表达，特别是 MBC 细胞中 HLA-A 或 B/C 的高表达，在预测 5 年生存率方面似乎具有非常高的特异性。我们确定了这些 HLA 分子簇的截断值，这些截断值具有高特异性，如果在更大的前瞻性队列中提高了其敏感性，可能有助于将其作为 5 年总生存率的预后标志物来识别预后良好的患者。
