Goerdt Lukas, Stefanovic Aleksandra, Wirtz Ralph, Karic Uros, Deutsch Thomas M, Kohler Maximilian, Schneeweiss Andreas, Sütterlin Marc, Stefanovic Stefan, Hofmann Jan, Wallwiener Markus
Department of Gynecology and Obstetrics, Mannheim University Hospital, Heidelberg University, Heidelberg, Germany.
Brüderklinikum Julia Lanz - Diakonissenkrankenhaus, Mannheim, Germany.
Anticancer Res. 2025 Feb;45(2):445-450. doi: 10.21873/anticanres.17433.
BACKGROUND/AIM: The loss of breast cancer cell differentiation during metastatic progression leads to a down-regulation of class 1 human leukocyte antigen (HLA) expression, which in turn hinders cytotoxic T lymphocytes from effectively preventing tumor cell proliferation. Consequently, one would expect that decreased HLA expression would correlate with decreased 5-year survival. However, estrogen receptor alpha (ESR1) is known to be positively associated with overall survival. The study aimed to determine the expression levels of HLA-A, HLA-B/C, and ESR1 and to assess their influence on distant disease-free survival (DDFS).
This retrospective subgroup analysis of the initial prospective, single-center, double-blind cohort study included a total of 34 patients who underwent a new treatment line for metastatic breast cancer (MBC). The MBC cells were examined using RT-qPCR.
The acquired data and the subsequent survival and ROC analyses indicated a positive association of reduced expression of HLA-A and HLA-B/C with DDFS. A statistically significant association of ESR1 with DDFS could not be shown.
A potential positive association between reduced expression of HLA-A and HLA-B/C and DDFS is observed. This contrasts with the generally observed association between HLA expression loss and poor prognosis, as reported in previous protein-based studies. In metastatic settings, reduced expression of particular HLA subsets, measured at the mRNA level, might have a protective effect against disease progression.
背景/目的:乳腺癌细胞在转移过程中分化丧失导致1类人类白细胞抗原(HLA)表达下调,进而阻碍细胞毒性T淋巴细胞有效阻止肿瘤细胞增殖。因此,可以预期HLA表达降低与5年生存率降低相关。然而,已知雌激素受体α(ESR1)与总生存期呈正相关。本研究旨在确定HLA-A、HLA-B/C和ESR1的表达水平,并评估它们对远处无病生存期(DDFS)的影响。
这项对最初的前瞻性、单中心、双盲队列研究的回顾性亚组分析共纳入了34例接受转移性乳腺癌(MBC)新治疗方案的患者。采用RT-qPCR检测MBC细胞。
获得的数据以及随后的生存分析和ROC分析表明,HLA-A和HLA-B/C表达降低与DDFS呈正相关。未显示ESR1与DDFS有统计学意义的关联。
观察到HLA-A和HLA-B/C表达降低与DDFS之间可能存在正相关。这与以往基于蛋白质的研究中普遍观察到的HLA表达缺失与预后不良的关联形成对比。在转移性情况下,在mRNA水平测量的特定HLA亚组表达降低可能对疾病进展具有保护作用。