Overexpression of CCL20 and its receptor CCR6 predicts poor clinical prognosis in human gliomas

Abstract

Recent studies have demonstrated that the chemokine CCL20 and its receptor CCR6 may be involved in tumorigenesis, tumor progression and metastatic spread of various human malignancies. The aim of this study was to investigate the clinicopathological significance and prognostic value of CCL20 and CCR6 expression in human malignant glioma. CCL20 and CCR6 expression in human gliomas and nonneoplastic brain tissues was measured by immunohistochemistry. The association of CCL20 and CCR6 expression with clinicopathological factors or prognosis in glioma patients was statistically analyzed. The expression levels of CCL20 and CCR6 proteins were both up-regulated in glioma tissues. There was a significantly positive correlation between the expression of the two markers (r = 0.88; P < 0.001). In addition, the overexpressions of CCL20 and CCR6 were both detected in high-grade glioma tissues compared with those in low-grade tissues and increased with ascending tumor World Health Organization (WHO) grades (P = 0.006 and 0.008, respectively). The increased expressions of CCL20 and CCR6 proteins were also significantly correlated with low Karnofsky performance score (both P = 0.01). Moreover, univariate analysis found that CCL20 expression (P = 0.002), CCR6 expression (P = 0.002) and CCL20/CCR6 co-expression (P < 0.001) were all significantly associated with poor prognosis. In particular, glioma patients with CCL20/CCR6 co-expression have the shortest overall survival. Multivariate analysis further identified the expression levels of CCL20 and CCR6 to be independent prognostic factors. Our data suggest for the first time that CCL20 and CCR6 might play an important role in the regulation of aggressiveness in human gliomas. The up-regulation of CCL20 and CCR6 might be closely associated with poor clinical outcome of patients with gliomas.

IMP-3 Promotes Migration and Invasion of Melanoma Cells by Modulating the Expression of HMGA2 and Predicts Poor Prognosis in Melanoma

“…To identify the potential targets of IMP-3, we examined the mRNA expression profile of IMP-3-overexpressed cells and identified transcripts upregulated by IMP-3 overexpression, which were previously identified to be involved in tumor progression (Tureci et al, 2002;Wang et al, 2012;Assi et al, 2013;Frewer et al, 2013;Ma et al, 2013;Raskin et al, 2013).…”

MicroRNA-150 inhibits tumor invasion and metastasis by targeting the chemokine receptor CCR6, in advanced cutaneous T-cell lymphoma

“…19,20,31,45,46 Notably, CCR6 is strongly associated with tumorigenesis, especially in advanced and metastatic cancer. 23,[33][34][35] In colorectal cancer, for example, upregulation of CCR6 in the tumor cells strongly correlates with liver metastasis and has proven to be an independent prognostic marker of the tumor entity. 22 These findings prompted us to hypothesize that CCR6 is a key regulator of invasion/metastasis in CTCL, and our results are consistent with that idea.…”

“…A total of 14 genes were commonly downregulated and 15 were commonly upregulated in the 3 CTCL cell lines ( Figure 4A). Among these, we considered the CCR6 gene and the product (CCR6) to be the most likely direct target of miR-150 because CCR6 is a chemokine receptor whose aberrant overexpression is strongly associated with tumor invasion and metastasis in solid tumors, [20][21][22][23] and upregulation of CCR6 was recently observed in advanced CTCL. 24 We, therefore, used qPCR to examine CCR6 expression in 12 samples of primary metastatic CTCL and found it to be significantly higher than in normal CD4…”

The chemokine receptor CCR6 facilitates the onset of mammary neoplasia in the MMTV-PyMT mouse model via recruitment of tumor-promoting macrophages

“…Interestingly, together with CCL20, CCR6 expression has been correlated with stage and prognosis in a variety of cancers including hepatocellular carcinoma [14, 15], colorectal carcinoma [16–18], glioma [19], and non-small cell lung cancer [20], and a function for CCR6 in regulation of cancer progression has been putatively demonstrated using cell lines and xenograft models [16, 18, 21, 22]. In breast cancer, higher CCR6 expression levels were linked with tumor stage and grade [23], and incidence of metastasis to the pleura [24].…”