Campos Amarilis de Lima, Sawada Maria Isabela Bloise Alves Caldas, Santana Monique Fátima de Mello, Iborra Rodrigo Tallada, de Assis Sayonara Ivana Santos, Reis Mozania, de Carvalho Jacira Xavier, Gebrim Luiz Henrique, Passarelli Marisa
Programa de Pós-Graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil.
Centro de Referência da Saúde da Mulher (Hospital Pérola Byington), São Paulo, Brazil.
Front Oncol. 2023 Mar 9;13:1111094. doi: 10.3389/fonc.2023.1111094. eCollection 2023.
The association between high-density lipoprotein cholesterol (HDLc) with the incidence and progression of breast cancer (BC) is controversial. HDL removes excess cholesterol from cells and acts as an antioxidant and anti-inflammatory. BC is a heterogeneous disease, and its molecular classification is important in the prediction of clinical and therapeutic evolution. Triple-negative breast cancer (TNBC) presents higher malignancy, lower therapeutic response, and survival rate. In the present investigation, the composition and antioxidant activity of isolated HDL was assessed in women with TNBC compared to controls.
Twenty-seven women with a recent diagnosis of TNBC, without prior treatment, and 27 healthy women (control group) paired by age and body mass index (BMI) were included in the study. HDL and low-density lipoprotein (LDL) were isolated from plasma by discontinuous density gradient ultracentrifugation. Plasma lipid profile and HDL composition (total cholesterol, TC; triglycerides, TG; HDLc; phospholipids, PL) were determined by enzymatic colorimetric methods. ApoB and apo A-I were quantified by immunoturbidimetry. The antioxidant activity of HDL was determined by measuring the lag time phase for LDL oxidation and the maximal rate of conjugated dienes formation in LDL incubated with copper sulfate solution. The absorbance (234 nm) was monitored at 37°C, for 4 h, at 3 min intervals.
The control group was similar to the TNBC concerning menopausal status, concentrations, and ratios of plasma lipids. The composition of the HDL particle in TC, TG, PL, and apo A-I was also similar between the groups. The ability of HDL to retard LDL oxidation was 22% greater in the TNBC group as compared to the control and positively correlated with apoA-I in HDL. Moreover, the antioxidant activity of HDL was greater in the advanced stages of TNBC (stages III and IV) compared to the control group. The maximum rate of formation of conjugated dienes was similar between groups and the clinical stages of the disease.
The results highlight the role of HDL as an antioxidant defense in TNBC independently of HDLc plasma levels. The improved antioxidant activity of HDL, reflected by retardation in LDL oxidation, could contribute to limiting oxidative and inflammatory stress in advanced stages of TNBC.
高密度脂蛋白胆固醇（HDLc）与乳腺癌（BC）的发生和进展之间的关联存在争议。HDL可清除细胞内多余的胆固醇，并具有抗氧化和抗炎作用。BC是一种异质性疾病，其分子分类对于预测临床和治疗进展具有重要意义。三阴性乳腺癌（TNBC）具有更高的恶性程度、更低的治疗反应率和生存率。在本研究中，我们评估了TNBC患者与对照组中分离出的HDL的组成和抗氧化活性。
本研究纳入了27例近期诊断为TNBC且未接受过治疗的女性，以及27例年龄和体重指数（BMI）相匹配的健康女性（对照组）。通过不连续密度梯度超速离心法从血浆中分离HDL和低密度脂蛋白（LDL）。采用酶比色法测定血浆脂质谱和HDL组成（总胆固醇、TC；甘油三酯、TG；HDLc；磷脂、PL）。通过免疫比浊法对载脂蛋白B（ApoB）和载脂蛋白A-I（apo A-I）进行定量。通过测量LDL氧化的延迟时间阶段以及与硫酸铜溶液孵育的LDL中共轭二烯形成的最大速率来测定HDL的抗氧化活性。在37°C下，每隔3分钟监测4小时的吸光度（234nm）。
对照组在绝经状态、血浆脂质浓度和比例方面与TNBC组相似。两组之间HDL颗粒在TC、TG、PL和apo A-I方面的组成也相似。与对照组相比，TNBC组中HDL延缓LDL氧化的能力高22%，且与HDL中的apoA-I呈正相关。此外，与对照组相比，TNBC晚期（III期和IV期）HDL的抗氧化活性更高。两组之间以及疾病的临床分期共轭二烯形成的最大速率相似。
结果突出了HDL在TNBC中作为抗氧化防御的作用，而与血浆HDLc水平无关。HDL抗氧化活性的提高表现为LDL氧化的延迟，这可能有助于在TNBC晚期限制氧化和炎症应激。
