Abstract
BackgroundHigh 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.MethodsA 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.ResultsA 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.ConclusionsThis 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.
Highlights
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
Inclusion and exclusion criteria Studies included in the present meta-analysis were independently reviewed by two investigators (XQ and DS) and should meet the following criteria: (1) The prognostic data of 8-OHdG in any type of human solid tumors needed to be presented; (2) All cancer patients were diagnosed according to the gold standard for diagnosis, based on histopathological examinations; (3) 8-OHdG levels in tumors, blood samples or urine were estimated in each study; (4) The patients were divided into two groups according to the levels of 8-OHdG; (5) Sufficient data should be provided to obtain hazard ratios (HR) for survival rates and their 95% confidence intervals (95%CI)
Further studies with uniform standards of detection assay and analysis method to evaluate the expression levels of 8-OHdG are required to elucidate the role of 8-OHdG in human cancers. This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors
Summary
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. Tumor cells constantly suffer various endogenous and environmental attacks, which make high level of reactive oxygen species (ROS) be detected in almost all cancers and become one of the best-characterized phenotypes [1,2,3]. High levels of ROS can play a role in tumor suppression by inhibiting cell proliferation and inducing cell death [7,8,9] Many cancer treatments, such as radiotherapy and certain chemotherapy agents, act through oxidative stress pathways via the production of ROS to suppress tumor growth and progression [10]. In order to prevent cell death, cancer cells can scavenge reactive oxygen species to adapt high levels of ROS and activate pro-tumorigenic signaling pathways, by upregulating antioxidant pathways and regulatory factors [11,12,13]
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