卵巢癌中的氧化还原生物标志物与基质重塑分子
Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer.
作者信息
Supruniuk Elżbieta, Baczewska Marta, Żebrowska Ewa, Maciejczyk Mateusz, Lauko Kamil Klaudiusz, Dajnowicz-Brzezik Patrycja, Milewska Patrycja, Knapp Paweł, Zalewska Anna, Chabowski Adrian
机构信息
Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland.
Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Marii Skłodowskiej-Curie 24A Street, 15-276 Bialystok, Poland.
出版信息
Antioxidants (Basel). 2024 Feb 4;13(2):200. doi: 10.3390/antiox13020200.
Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.
卵巢癌(OC)已成为女性妇科恶性肿瘤致死的主要原因。氧化应激和金属蛋白酶(MMPs)已被证明会影响信号通路并影响致癌作用的进展。因此,评估基质重塑和氧化应激强度可以确定细胞损伤程度以及氧化还原介导的化疗耐药性的严重程度。研究组包括27例浆液性OC患者,其中18%被归类为国际妇产科联盟(FIGO)I/II期,其余被诊断为III/IV级。对照组由15个卵巢组织样本组成。将结果与来自癌症基因组图谱的基因数据进行比较。在原发性卵巢肿瘤和健康组织中,采用比色法/荧光法或通过实时PCR检测硝基氧化应激、炎症和凋亡生物标志物。根据FIGO分期对患者进行分层显示,高级别癌在氧化还原平衡方面表现出显著改变,包括蛋白质糖氧化和脂质过氧化产物的积累。TCGA数据显示所研究基因的预后价值有限。总之,高级别浆液性OC与组织氧化/亚硝化应激增强和大分子损伤相关,而同时增强的抗氧化防御措施无法克服这种损伤。因此,可以假设肿瘤细胞获得了使其能够抵御活性氧升高潜在毒性作用的适应性机制。