Veljkovic Andrej, Stanojevic Goran, Brankovic Branko, Roumeliotis Stefanos, Leivaditis Konstantinos, Djordjevic Branka, Li Xiaobo, Klisic Aleksandra, Hadzi-Djokic Jovan, Kocic Gordana
Faculty of Medicine, University of Nis, 18000 Nis, Serbia.
Clinical Center, 18000 Nis, Serbia.
Curr Issues Mol Biol. 2025 Jul 17;47(7):557. doi: 10.3390/cimb47070557.
Colorectal cancer (CRC) is characterized by complex interactions between inflammation, oxidative stress, and extracellular matrix remodeling. Recent studies have highlighted the significance of the reactive oxygen species (ROS)-nuclear factor kappa B (NF-κB)-matrix metalloproteinase-9 (MMP-9) axis in promoting tumor invasion and metastasis in CRC, linking oxidative stress with inflammatory signaling and extracellular matrix degradation. In this study, we analyzed the concentration of advanced oxidation protein products (AOPPs), expression of NF-κB, and the activity of MMP-9 in tumor tissue, adjacent tissue, and healthy control colon tissue. Tissue specimens were collected from 50 patients with primary CRC following surgical resection. The analyses were performed using appropriate and validated biochemical methods, including ELISA, spectrophotometry, and indirect immunofluorescence. Significantly higher levels of all three markers were observed in tumor tissue compared to controls. Additionally, adjacent tissue exhibited elevated NF-κB expression and MMP-9 activity when compared to healthy colon tissue. AOPP levels correlated strongly with MMP-9 activity, highlighting the role of oxidative stress in the activation of MMP-9. MMP-9 demonstrated the highest predictive value for CRC, emphasizing its potential as a diagnostic and theranostic marker. Our findings support the hypothesis that the ROS-NF-κB-MMP-9 axis plays an important role in CRC progression, particularly during stages T2 and T3. Targeting this pathway may offer new therapeutic strategies for limiting tumor invasion and recurrence. Moreover, ensuring adequate surgical resection margins is crucial to optimizing treatment outcomes.
结直肠癌（CRC）的特征是炎症、氧化应激和细胞外基质重塑之间存在复杂的相互作用。最近的研究强调了活性氧（ROS）-核因子κB（NF-κB）-基质金属蛋白酶-9（MMP-9）轴在促进CRC肿瘤侵袭和转移中的重要性，将氧化应激与炎症信号传导和细胞外基质降解联系起来。在本研究中，我们分析了肿瘤组织、相邻组织和健康对照结肠组织中晚期氧化蛋白产物（AOPPs）的浓度、NF-κB的表达以及MMP-9的活性。从50例接受手术切除的原发性CRC患者中收集组织标本。使用适当且经过验证的生化方法进行分析，包括酶联免疫吸附测定（ELISA）、分光光度法和间接免疫荧光法。与对照组相比，在肿瘤组织中观察到所有三种标志物的水平均显著更高。此外，与健康结肠组织相比，相邻组织中NF-κB的表达和MMP-9的活性有所升高。AOPP水平与MMP-9活性密切相关，突出了氧化应激在MMP-9激活中的作用。MMP-9对CRC表现出最高的预测价值，强调了其作为诊断和治疗诊断标志物的潜力。我们的研究结果支持以下假设：ROS-NF-κB-MMP-9轴在CRC进展中起重要作用，特别是在T2和T3期。靶向该途径可能为限制肿瘤侵袭和复发提供新的治疗策略。此外，确保足够的手术切缘对于优化治疗结果至关重要。
