Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara 06100, Turkey.
İstanbul Education and Research Hospital, Obstetrics and Gynecology, İstanbul 34020, Turkey.
J Trace Elem Med Biol. 2019 Mar;52:254-262. doi: 10.1016/j.jtemb.2019.01.010. Epub 2019 Jan 16.
Epithelial ovarian cancer (EOC) has been associated with oxidative stress (OS) due to epithelial inflammation which makes ovaries more vulnerable to the deleterious effects of reactive oxygen species (ROS). However, antioxidant enzymes (AOEs) such as manganese-superoxide dismutase (Mn-SOD), copper,zinc-superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GPx1) protect cells against the biological damage of ROS-induced OS and support cancer prevention by maintaining normal cell cycle progression, inhibiting proliferation, tumor invasion, angiogenesis, inflammation or inducing apoptosis. In the present study, we aimed to measure the levels of trace elements [manganese (Mn), copper (Cu), zinc (Zn) and selenium (Se)] which are structurally and/or functionally associated with the AOEs by inductively coupled plasma/mass-spectrometry (ICP/MS) in blood samples of patients with EOC (M, n = 26) and compare the data with healthy subjects (C, n = 46). Serous EOC (M1, n = 18) data were also evaluated according to the tumor grading [well or moderately well differentiated (G 1-2) vs. poorly differentiated or undifferentiated (G3)] and staging of disease [stage I-II (SI-II) vs. stage III (SIII)]. We obtained; i) The Mn and Se levels of M were significantly lower than C, ii) only Mn levels were changed [(G3 < G 1-2 ] in M1, iii) significant correlations were observed between [Cu and Zn levels (r = 0.701, p = 0.036) in G 1-2 and (r = 0.686, p = 0.041) in G3; Cu and Se levels (r = 0.960, p = 0.000) in G3; Mn levels and Mn-SOD expression (r = 0.551, p = 0.006) in M, (r = 0.857, p = 0.007) in G 1-2 and (r = 0.690, p = 0.056) in G3; Se levels and erythrocyte GPx1 activity (r = 0.660, p = 0.053) in G 1-2 ; Se levels and erythrocyte Cu,Zn-SOD activity (r = 0.693, p = 0.038) in G3]. The study revealed that trace elements, particularly low Mn and Se levels along with high Cu/Se ratios might be of value in all histologic subtypes of EOC. Although Mn level was important in terms of discriminating tumor grades, positive correlation between Cu-Se levels was also remarkable in patients with G 1-2 tumors of M1. Moreover, high erythrocyte Cu/Se ratios might be a favourable marker for EOC.
上皮性卵巢癌 (EOC) 与上皮炎症引起的氧化应激 (OS) 有关,这使卵巢更容易受到活性氧 (ROS) 的有害影响。然而,抗氧化酶 (AOEs),如锰超氧化物歧化酶 (Mn-SOD)、铜锌超氧化物歧化酶 (Cu,Zn-SOD) 和谷胱甘肽过氧化物酶 (GPx1),通过维持正常的细胞周期进程、抑制增殖、肿瘤侵袭、血管生成、炎症或诱导细胞凋亡,保护细胞免受 ROS 诱导的 OS 的生物损伤,并支持癌症预防。在本研究中,我们旨在通过电感耦合等离子体质谱 (ICP/MS) 测量 EOC 患者 (M,n=26) 血液样本中与 AOEs 结构和/或功能相关的微量元素[锰 (Mn)、铜 (Cu)、锌 (Zn) 和硒 (Se)]水平,并将数据与健康受试者 (C,n=46) 进行比较。根据肿瘤分级[高分化或中分化 (G1-2) 与低分化或未分化 (G3)]和疾病分期[I-II 期 (SI-II) 与 III 期 (SIII)],还评估了浆液性 EOC (M1,n=18) 的数据。我们得到了以下结果:i)M 的 Mn 和 Se 水平明显低于 C,ii)仅 Mn 水平发生变化[G3 < G1-2]在 M1 中,iii)在 G1-2 中观察到 [Cu 和 Zn 水平之间存在显著相关性 (r=0.701,p=0.036) 和 G3 (r=0.686,p=0.041);Cu 和 Se 水平之间存在显著相关性 (r=0.960,p=0.000) 在 G3 中;Mn 水平和 Mn-SOD 表达之间存在显著相关性 (r=0.551,p=0.006) 在 M 中,(r=0.857,p=0.007) 在 G1-2 中,(r=0.690,p=0.056) 在 G3 中;Se 水平与红细胞 GPx1 活性之间存在显著相关性 (r=0.660,p=0.053) 在 G1-2 中;Se 水平与红细胞 Cu,Zn-SOD 活性之间存在显著相关性 (r=0.693,p=0.038) 在 G3 中。研究表明,微量元素,特别是 Mn 和 Se 水平较低,以及高 Cu/Se 比值,可能对 EOC 的所有组织学亚型都有价值。尽管 Mn 水平在区分肿瘤分级方面很重要,但在 M1 的 G1-2 肿瘤患者中,Cu-Se 水平之间的正相关也很显著。此外,高红细胞 Cu/Se 比值可能是 EOC 的一个有利标志物。