Background: Cancer is a leading cause of death worldwide. At present, several inhibitors of bromodomain protein 4 have shown promising anti-tumor responses in clinical trials. Numerous studies have reported the value of bromodomain protein 4 expression in predicting the prognosis of patients with cancers, but their conclusions remain controversial. Therefore, we conducted a meta-analysis to explore the association between bromodomain protein 4 and patient prognosis with the aim to provide new directions for the development of strategies for targeted cancer therapy.
Methods: The meta-analysis was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/; Registration No. CRD42020184948) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. PubMed Central, PubMed, Cochrane Library and Embase were thoroughly searched to identify eligible studies published through March 31, 2021. Odds ratios with 95% confidence intervals were calculated to demonstrate the relationship between bromodomain protein 4 expression and clinicopathological features. We computed pooled estimated hazard ratios with 95% confidence intervals using Stata 12.0 software to clarify the relationship between bromodomain protein 4 expression and overall survival of various cancers. A quality assessment of the eligible articles was performed based on the Newcastle-Ottawa scale.
Results: A total of 974 patients from 10 studies were enrolled in the meta-analysis. Our results revealed that compared to low bromodomain protein 4 expression, high bromodomain protein 4 expression in cancer tissues was significantly associated with lymph node metastasis (Odds ratio = 3.59, 95% confidence interval: 2.62-4.91), distant metastasis (Odds ratio = 4.22, 95% confidence interval: 2.40-7.45), advanced TNM stage (III+IV vs. I+II: Odds ratio = 3.23, 95% confidence interval: 1.29-8.08), and poorly differentiated tumors (Odds ratio = 1.87, 95% confidence interval: 1.33-2.63). In addition, an elevated expression of bromodomain protein 4 tended to shorten survival time (Hazard ratio = 2.23, 95% confidence interval: 1.62-3.07). The subgroup analysis results showed that bromodomain protein 4 upregulation was related to poor prognosis in patients with digestive system cancers (Hazard ratio = 2.54, 95% confidence interval: 1.85-3.50).
Conclusion: This meta-analysis indicated that bromodomain protein 4 may serve as a promising prognostic biomarker for cancers and a direct effective cancer treatment target.
Keywords: BRD4; Cancer; Immunohistochemistry; Meta-analysis; Prognosis.
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