Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, 450052, China.
BMC Cancer. 2019 Oct 24;19(1):997. doi: 10.1186/s12885-019-6189-9.
High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to 2'-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear.
A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value.
A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437-2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482-3.005) using Cox multivariate analyses.
This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research.
活性氧(ROS)水平在几乎所有癌症中都有检测到,这使其成为癌症中特征最为明确的表型之一。尽管 ROS 在肿瘤中发挥重要作用,但由于其高度不稳定性,评估氧化反应的稳定代谢产物可以更好地评估氧化应激程度。8-羟基-2'-脱氧鸟苷(8-OHdG)是 2'-脱氧鸟苷氧化损伤的产物,作为评估氧化 DNA 损伤的有用标志物,已在多项研究中成为癌症发生的特征之一。但是,8-OHdG 表达在癌症患者中的确切预后价值仍不清楚。
在 PubMed、Web of Science 和 EMBASE 中进行了全面检索。根据明确的排除和纳入标准,纳入了符合条件的研究进行荟萃分析。使用 STATA 14.0 估计合并风险比(HR)及其 95%置信区间(95%CI)、研究间异质性和发表偏倚,以判断预后价值。
共有 21 项符合条件的研究中的 2121 名患者纳入荟萃分析。结果发现,癌症患者中 8-OHdG 表达升高与总生存期(OS)不良显著相关(合并 HR 1.921,95%CI:1.437-2.570);在亚组分析中,样本的种族、癌症类型、8-OHdG 的检测方法、样本分类、8-OHdG 的检测部位和论文质量(评分大于或小于 7)并未改变 8-OHdG 表达与癌症预后之间的关联。此外,Cox 多因素分析显示,8-OHdG 表达是癌症患者总生存的独立预后标志物(合并 HR 2.110,95%CI:1.482-3.005)。
本荟萃分析发现,肿瘤组织中 8-OHdG 高表达可能是大多数实体肿瘤预后的预测指标。然而,特别是在乳腺癌中,低 8-OHdG 表达与不良预后相关,这部分是由于乳腺癌组织中抗氧化机制增加所致。本研究首次证明 8-OHdG 表达与癌症患者的预后相关。未来,8-OHdG 的表达水平是否可以作为所有人类癌症预后的生物标志物,还需要更多的研究。