The Prognostic Value of CXCR4 in Ovarian Cancer: A Meta-Analysis

Cheng-Fei Liu,Yuan-Yuan Ji,Xiao-Yun Min,Ke Li,Shu-Yan Liu,Dan Liu,Ning Ma,Na Wang,Zong-Fang Li,Zoran Culig

doi:10.1371/journal.pone.0092629

Abstract

ObjectiveRecent reports have shown that C-X-C chemokine receptor 4 (CXCR4) is expressed in ovarian cancer and plays an important role in metastasis. However, the prognostic value of CXCR4 in ovarian cancer remains controversial and has not been emphasized. The aim of this study is to evaluate the prognostic significance of CXCR4 in ovarian cancer by performing a meta-analysis.MethodsWe systematically searched for studies evaluating the relationship between CXCR4 expression and the outcome of ovarian cancer patients. Only articles in which CXCR4 expression was detected by immunohistochemical staining were included. Hazard ratios (HRs) and relative risk (RR) with 95% confidence intervals (CIs) were pooled as effect size (ES) across studies for overall survival (OS) and progression-free survival (PFS).ResultsA total of 729 patients from 7 studies (6 articles) were included in this meta-analysis. Our results showed that high CXCR4 expression was significantly associated with poor prognosis in terms of OS (ES, 2.81; 95% CI, 1.16–6.80; p = 0.022) and PFS (ES, 8.48; 95% CI, 2.13–33.70; p = 0.002) in ovarian cancer patients. The association between high CXCR4 expression and poor ovarian cancer prognosis in OS was also statistically significant in subgroups of Asian and III-IV patients constituting 70%.ConclusionsThe present meta-analysis indicated that high CXCR4 expression was associated with poor prognosis in ovarian cancer. More studies, especially larger scale and well-matched researches, are warranted to clarify the prognostic effect of CXCR4 on the outcome of ovarian cancer.

Highlights

Ovarian cancer is the fifth leading cause of cancer deaths occurring in women and leading cause of mortality from gynecologic cancer [1], with epithelial cancer being responsible for 90% of ovarian malignancies
Criteria for Inclusion and Exclusion Studies eligible for inclusion in this meta-analysis met the following criteria in order to ensure the high quality of this article: (1) patients with distinctive ovarian cancer diagnosis by pathology; (2) CXCR4 expression was measured by immunohistochemistry (IHC) method; (3) full length paper with sufficient data on survival and CXCR4 expression
Among all of the included studies, Hazard ratios (HRs) or relative risk (RR) and 95% confidence intervals (CIs) were obtained from the original articles directly in 4 studies

Summary

Introduction

Ovarian cancer is the fifth leading cause of cancer deaths occurring in women and leading cause of mortality from gynecologic cancer [1], with epithelial cancer being responsible for 90% of ovarian malignancies. Ovarian cancer is among the most chemosensitive malignancies, and the currently established therapy of ovarian cancer includes radical surgical tumor debulking and subsequent platinum plus paclitaxel-based chemotherapy, the prognosis is still poor and the 5-year survival rate remains only 25% [2]. It is necessary to identify prognostic factors to predict the outcomes of patients, which could be effective in making strategies and improving survival for ovarian cancer. Traditional clinicopathological parameters, such as age, tumor histology, performance status and residual tumor volume are considered as independent predictors of prognosis in ovarian cancer [3,4]. Identifying molecular biological prognostic factors could enable to predict patients’ outcomes more accurately and provide novel therapeutic targets

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Results

Conclusion