Valcarenghi Jabonski Eduarda, Triquez Simone Luciana, Geraldi Norbah Ana Paula, Manica Daiane, Tessaro da Silva Keroli Eloiza, Fialho Cunha Karlla Rackell, Moreira Cordeiro Nagilla, Moreno Marcelo, Tavares de Resende E Silva Débora, Franco Vieira de Oliveira Maciel Sarah
Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
Graduate Program in Biochemistry, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Purinergic Signal. 2025 Sep 2. doi: 10.1007/s11302-025-10110-w.
Breast cancer (BC) is a multifactorial disease characterized by cell cycle disorder and immune evasion. Studies reveal that the purinergic system (PS) is a mediator of the immune system and actively participates in the inflammatory process in cancer. Also, there is growing debate about the role of oxidative stress (OS) markers and interleukins as predictors of BC progression and invasion. Thus, PS and OS markers, in addition to the expression of interleukins and quantification of extracellular ATP, were evaluated in 39 BC patients, before the beginning of surgical or pharmacological treatment, and in 35 control participants, matched by sex and age. The results show reduced ATP and ADP hydrolysis in platelets, apart from increased extracellular ATP in the BC group. Increased AMP hydrolysis was observed in BC patients' peripheral blood mononuclear cells (PBMCs). BC patients presented elevated oxidative parameters (MDA) and reduced antioxidant parameters (SOD and ascorbic acid), and reduction in interleukins TNF, IL-4, and IL-2. In PBMC from the BC group, the expression of P2X7 gene was significantly higher in relation to the expression of CD39 gene. Also, the expression of CD39 was 1.71 fold higher in tumor samples compared to PBMC from the BC group, and it was 0.11 fold lower in PBMC from the BC group compared to the controls. We conclude that ectoenzymes that hydrolyze ATP and ADP, mainly CD39, present reduced activity in the BC group, promoting an increase in extracellular ATP and culminating in a pro-inflammatory environment, favoring cancer progression. The increase in active oxidants and the reduction in antioxidants contributed to the progression of BC in patients. Finally, TNF and IL-4 demonstrated to be promising prognostic markers in BC patients.
乳腺癌（BC）是一种多因素疾病，其特征为细胞周期紊乱和免疫逃逸。研究表明，嘌呤能系统（PS）是免疫系统的介质，并积极参与癌症的炎症过程。此外，关于氧化应激（OS）标志物和白细胞介素作为BC进展和侵袭预测指标的作用，争议也越来越大。因此，在39例BC患者手术或药物治疗开始前，以及35例按性别和年龄匹配的对照参与者中，对PS和OS标志物以及白细胞介素的表达和细胞外ATP的定量进行了评估。结果显示，除了BC组细胞外ATP增加外，血小板中ATP和ADP水解减少。在BC患者外周血单个核细胞（PBMC）中观察到AMP水解增加。BC患者氧化参数（MDA）升高，抗氧化参数（SOD和抗坏血酸）降低，白细胞介素TNF、IL-4和IL-2减少。在BC组的PBMC中，P2X7基因的表达相对于CD39基因的表达显著更高。此外，与BC组的PBMC相比，肿瘤样本中CD39的表达高1.71倍，与对照组相比，BC组PBMC中CD39的表达低0.11倍。我们得出结论，水解ATP和ADP的胞外酶，主要是CD39，在BC组中活性降低，导致细胞外ATP增加，最终形成促炎环境，有利于癌症进展。活性氧化剂的增加和抗氧化剂的减少促成了患者BC的进展。最后，TNF和IL-4被证明是BC患者有前景的预后标志物。
