Galiniak Sabina, Biesiadecki Marek, Mołoń Mateusz, Olech Patrycja, Balawender Krzysztof
Institute of Medical Sciences, Medical College, Rzeszow University, Warzywna 1a, 35-310 Rzeszow, Poland.
Institute of Biology, College of Natural Sciences, Rzeszow University, Zelwerowicza 4, 35-601 Rzeszow, Poland.
Cancers (Basel). 2023 Aug 7;15(15):3995. doi: 10.3390/cancers15153995.
Oxidative stress is believed to be a factor in the development and progression of renal cell carcinoma (RCC). The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell RCC (ccRCC) may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. This study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. The studied group consisted of 48 newly diagnosed ccRCC and 30 healthy controls. Serum levels of oxidative stress markers-advanced oxidation protein products (AOPP), thiol groups, Amadori reaction products, 3-nitrotyrosine, nitrate/nitrite, malondialdehyde (MDA), 4-hydroxy-2-nonenal and total antioxidant capacity (TAC)-were determined. Additionally, associations between tumour stage assessed according to TNM classification, histological grade, and the effect of the presence of angioinvasion on the level of stress markers were evaluated. The levels of Amadori products, 3-nitrotyrosine, and nitrate/nitrite were elevated, while the levels of thiol groups and TAC decreased in the ccRCC group. The levels of AOPP, Amadori, and 3-nitrotyrosine increased, and thiol groups and TAC levels decreased with the increasing pathological stage of the tumour. In the case of advanced histological assessment of the tumour, we found decreasing levels of thiol groups and increasing levels of MDA. In patients with angioinvasion, nitrate/nitrite and MDA levels were significantly elevated compared to those in patients without angioinvasion. Oxidative stress increased with the progression of the disease assessed according to the TNM and histological grade. These results demonstrate systemic oxidative stress in ccRCC, suggesting the therapeutic application of antioxidants.
氧化应激被认为是肾细胞癌(RCC)发生和发展的一个因素。鉴定蛋白质的氧化和亚硝化修饰及其在透明细胞肾细胞癌(ccRCC)中的作用,可能有助于制定减轻蛋白质损伤的靶向治疗方法。本研究旨在调查氧化/亚硝化应激状态,并探讨其在ccRCC发生和发展中的作用。研究组包括48例新诊断的ccRCC患者和30例健康对照。测定了血清氧化应激标志物——晚期氧化蛋白产物(AOPP)、巯基、阿马多里反应产物、3-硝基酪氨酸、硝酸盐/亚硝酸盐、丙二醛(MDA)、4-羟基壬烯醛和总抗氧化能力(TAC)的水平。此外,还评估了根据TNM分类评估的肿瘤分期、组织学分级以及血管侵犯的存在对应激标志物水平的影响之间的关联。ccRCC组中阿马多里产物、3-硝基酪氨酸和硝酸盐/亚硝酸盐水平升高,而巯基和TAC水平降低。随着肿瘤病理分期的增加,AOPP、阿马多里产物和3-硝基酪氨酸水平升高,巯基和TAC水平降低。在肿瘤组织学评估为高级别时,我们发现巯基水平降低,MDA水平升高。与无血管侵犯的患者相比,有血管侵犯的患者中硝酸盐/亚硝酸盐和MDA水平显著升高。根据TNM和组织学分级评估,氧化应激随着疾病进展而增加。这些结果表明ccRCC中存在全身性氧化应激,提示抗氧化剂的治疗应用。