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.
氧化应激被认为在肾透明细胞癌(ccRCC)的发生和进展中起一定作用。鉴定蛋白质的氧化和亚硝基化修饰并明确其在ccRCC中的作用,可能有助于制定靶向治疗策略以减轻蛋白质损伤。本研究旨在评估氧化/亚硝基化应激状态并探讨其在ccRCC发展中的作用。研究对象包括48例新确诊的ccRCC患者和30例健康对照者,检测其血清氧化应激标志物水平,包括晚期氧化蛋白产物(AOPP)、硫醇基团、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-2-壬烯醛和总抗氧化能力(TAC)。同时评估肿瘤TNM分期、组织学分级、血管浸润与应激标志物水平的关系。结果显示,ccRCC组阿马多里产物、3-硝基酪氨酸和硝酸盐/亚硝酸盐水平升高,而硫醇基团和TAC水平下降。AOPP、阿马多里产物和3-硝基酪氨酸水平随肿瘤病理分期升高而增加,而硫醇基团和TAC水平呈下降趋势。在肿瘤组织学分级评估中,发现硫醇基团水平随恶性程度增加而降低,MDA水平升高。血管浸润阳性患者的硝酸盐/亚硝酸盐和MDA水平显著高于无血管浸润患者。根据TNM分期和组织学分级评估的疾病进展程度与氧化应激水平呈正相关。上述结果表明ccRCC患者存在全身性氧化应激,提示抗氧化剂具有潜在治疗应用价值。
Serum Oxidative and Nitrosative Stress Markers in Clear Cell Renal Cell Carcinoma