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The prognostic value of CXC chemokine receptor 2 (CXCR2) in cancers: a meta-analysis.

ABSTRACT: Quite a few studies had investigated the correlation between CXC chemokine receptor 2 (CXCR2) and cancer. This meta-analysis was aimed to comprehensively summarize the previous studies and to explore the prognostic value of CXCR2 in patients with cancer.An adequate literature search in EMBASE and PubMed was conducted. Articles in English which have reported CXCR2 expression in patients and enough data to calculate hazard ratio (HR) were included. Effect estimates were analyzed with Review Manager 5.2. The endpoint was overall survival (OS) and recurrence-free survival (RFS).Twelve studies from 10 publications with a total of 2,461 patients were identified. It was shown that high level of CXCR2 was significantly associated with poorer overall survival (OS) (HR = 1.69, 95% CI = 1.46-1.96, p < 0.0001, I2 = 45%) and RFS (HR = 1.50, 95% CI = 1.25-1.80, p < 0.0001, I2 = 6%). The analyses of different analysis models (univariate or multivariate models), sample size (< 300 or ≥ 300) and ethnicity (Asian and Caucasian) have indicated the negative impact of CXCR2 over-expression on survival of patients with cancer. Stratified by cancer type, high-expression of CXCR2 was associated with unfavorable OS in laryngeal squamous cell carcinoma, lung cancer, pancreatic ductal carcinoma, clear-cell renal cell carcinoma and hepatocellular carcinoma; however, there was significant difference between high- and low-expression of CXCR2 in digestive tract cancer (esophageal adenocarcinoma and squamous cell carcinoma procession, resected esophageal carcinoma, esophageal cancer and gastric cancer).CXCR2 is an unfavorable predictor in terms of OS and RFS in patients with cancer except for digestive tract cancer and is related with poorer prognostic.

SUBMITTER: Qiao B

PROVIDER: S-EPMC5871098 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC.MethodsIn this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases.ResultsBoth CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis.ConclusionsOur findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia.

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The prognostic value of CXC chemokine receptor 2 (CXCR2) in cancers: a meta-analysis.

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