Tarhonska Kateryna, Wichtowski Mateusz, Wow Thomas, Kołacińska-Wow Agnieszka, Płoszka Katarzyna, Fendler Wojciech, Zawlik Izabela, Paszek Sylwia, Zuchowska Alina, Jabłońska Ewa
Department of Translational Research, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348 Lodz, Poland.
Department of Surgical Oncology, Institute of Oncology, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland.
Biomedicines. 2025 Feb 26;13(3):585. doi: 10.3390/biomedicines13030585.
Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited treatment options due to the absence of estrogen, progesterone receptors, and HER2 expression. This study examined the impact of DNA methylation and demethylation markers in tumor tissues on TNBC patients' response to neoadjuvant chemotherapy (NACT) and analyzed the correlation between 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) and clinicopathological characteristics, offering new insights into the predictive value of these epigenetic markers. The study included 53 TNBC female patients, 19 of whom received neoadjuvant chemotherapy (NACT) before surgery. Global DNA methylation and demethylation levels were quantified using an ELISA-based method to measure 5-mC and 5-hmC content in DNA isolated from pre-treatment biopsy samples (in patients undergoing NACT) and postoperative tissues (in patients without NACT). In patients who received NACT, those with disease progression had significantly higher pretreatment levels of 5-hmC ( = 0.028) and a trend toward higher 5-mC levels ( = 0.054) compared to those with pathological complete response, partial response, or stable disease. Higher 5-mC and 5-hmC levels were significantly associated with higher tumor grade ( = 0.039 and = 0.017, respectively). Additionally, a positive correlation was observed between the Ki-67 proliferation marker and both 5-mC (r = 0.340, = 0.049) and 5-hmC (r = 0.341, = 0.048) levels in postoperative tissues. Our study highlights the potential of global DNA methylation and demethylation markers as predictors of tumor aggressiveness and chemotherapy response in TNBC. Further research in larger cohorts is necessary to validate these markers' prognostic and predictive value.
三阴性乳腺癌（TNBC）是一种侵袭性癌症亚型，由于缺乏雌激素、孕激素受体以及HER2表达，其治疗选择有限。本研究检测了肿瘤组织中的DNA甲基化和去甲基化标志物对TNBC患者新辅助化疗（NACT）反应的影响，并分析了5-甲基胞嘧啶（5-mC）和5-羟甲基胞嘧啶（5-hmC）与临床病理特征之间的相关性，为这些表观遗传标志物的预测价值提供了新见解。该研究纳入了53例TNBC女性患者，其中19例在手术前接受了新辅助化疗（NACT）。采用基于酶联免疫吸附测定（ELISA）的方法对整体DNA甲基化和去甲基化水平进行定量，以测量从治疗前活检样本（接受NACT的患者）和术后组织（未接受NACT的患者）中分离出的DNA中的5-mC和5-hmC含量。在接受NACT的患者中，与病理完全缓解、部分缓解或病情稳定的患者相比，疾病进展的患者治疗前5-hmC水平显著更高（P = 0.028），5-mC水平有升高趋势（P = 0.054）。更高的5-mC和5-hmC水平与更高的肿瘤分级显著相关（分别为P = 0.039和P = 0.017）。此外，在术后组织中观察到Ki-67增殖标志物与5-mC（r = 0.340，P = 0.049）和5-hmC（r = 0.341，P = 0.048）水平均呈正相关。我们的研究强调了整体DNA甲基化和去甲基化标志物作为TNBC肿瘤侵袭性和化疗反应预测指标的潜力。有必要在更大的队列中进行进一步研究以验证这些标志物的预后和预测价值。
