| Objective:Recently, the chemokine receptor CXCR4 has been widely investigated and is gradually proposed as an effective biological target for the treatment of many tumors. At the same time, there are more and more studies focusing on the relationship between CXCR4 expression and WHO grade, prognosis of gliomas. However the results from different studies are controversial. In order to clarify these relationships, we used the immunohistochemistry to detect the expression of CXCR4, and then analyzed the associations between CXCR4 and WHO grade, prognosis. Furthermore, we included the relevant articles to carry out meta-analysis and systematic review, which can elucidate the real role of CXCR4 in diagnosis and treatment of glioma.Methods:1. We used the immunohistochemistry to detect the expression of CXCR4 in 60 cases of glioma tissues, and analyzed the associations between CXCR4 and clinical pathological indicators.2. Search terms, "human glioma", "chemokine receptor CXCR4" or "CXCR4", "prognosis", "expression", are used to formulate retrieval words by the "AND/OR/NOT" connection, and then literature was searched using CNKI, Wanfang database, PUBMED, and Google Scholar et al database.3. We searched articles officially published or published online until October,2014, and then selected articles depending on the inclusion and exclusion criteria. All references in retrieved articles were also scanned to identify other potentially available reports.4. Using the European Lung Cancer Working Party (ELWCP) assessment criteria to finish quality assessment on the included articles, and then extracted data from the included articles and did Meta analysis using the fixed effect model by STATA 10.0 software, and chose the fixed or random effect model depending on the heterogeneity result of Q test, and used the Z test to calculate the P value of the final result.5. We used the meta regression analysis and subgroup analysis method to investigate the source of the heterogeneity. Publication bias was detected through funnel plot, Egger and Begger test. At last, the stability of the result was further verified by sensitivity analysis.Results:1. In all 60 cases of gliomas, the positive rate of CXCR4 is 75.0% (45/60). In glioma tissues with high WHO grade (Ⅲ+Ⅳ), the expression rate of CXCR4 was 96.0% (24/25), however, in gliomas with low grade, the positive rate of CXCR4 is 60.0% (21/35); differences were significant (p＜0.01). CXCR4 expression was not associated with age, gender.2. Initially, a structured literature search generated 170 articles. According to statistic data, study type, study contents and reduplications, eventually,13 case-control articles with 785 patients were included and there was no omission in the references in retrieved articles.2. No low quality articles were found through quality assessment.10 studies used dichotomous method, and the combined results showed that in glioma, the high expression of CXCR4 is obviously related with the high grading of glioma (OR=5.46, 95%CI 3.81-7.84; p=0.000). At the same time,6 studies used the continuous variable also demonstrated that the expression of CXCR4 is related with the grading of glioma (SMD=-2.45,95% CI-2.78,-2.12; p=0.000).3. There are three articles included showed that CXCR4 is related with the prognosis of glioma. The pooled results indicated that the expression of CXCR4 is obviously related with the 3 years overall survival rate (OS) of glioma patient (HR=7.32,95% CI4.16-12.90; p=0.000).4. No heterogeneity was found in this meta-analysis (p>0.1); the regression analysis further verified that the age, gender and nationality of the patient have no influence on the statistics of CXCR4 and pathological grading of glioma. Begger and Egger analysis showed that no statistical publication bias was found in included articles; at the same time, the sensitivity analysis also confirmed that no bias happened in the final result after deleting any of the included articles.Conclusions:1. In our study, results from 60 cases of glioma tissues and meta-analysis suggested that the high expression of CXCR4 is closely related with the grade of glioma, and has an obvious significance on the prognosis of gliomas. This meta analysis will offer a new direction for the application of CXCR4 in the clinical practice as a molecular biomarker in the grade and prognosis of gliomas, and can also provide a theoretical basis for the biological target treatment of glioma by targeting CXCR4.2. Further studies, such as more samples, multicenter prospective cohort studies or randomized controlled trials (RCTs), are required to eventually certify the significance of CXCR4 on grading and prognosis of glioma and to verify whether CXCR4 is the independent risk factor for the development of glioma. |
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