Wang et al. Journal of Experimental & Clinical Cancer Research 2012, 31:44 http://www.jeccr.com/content/31/1/44 Page 6 of 7 Figure 3 Kaplan-Meier survival curves for glioma patients with high CLIC1 expression versus low CLIC1 expression. (A) The cumulative 5-year overall survival was significantly shorter for patients with high CLIC1 expression than those with low CLIC1 expression (P<0.001). (B and C) Kaplan-Meier analysis showing the overall survival of glioma patients categorized according to the WHO grading criteria and status of CLIC1 expression. The cumulative 5-year overall survival was significantly different between high CLIC1 expression and low CLIC1 expression patients within subgroups of WHO Grades I~II (B, P=0.01) and III~IV (C, P=0.008). As a member of the CLIC family, CLIC1 functions as a real chloride channel in plasma and nuclear mem- branes [19]. The distribution of intracellular CLIC1 ex- pression varies depending on the cell types, from intracellular vesicular pattern to intranuclear distribu- tion. Its physiological roles include ion homeostasis modulation, cell volume regulation, transepithelial trans- port, and regulation of electrical excitability [20]. Accu- mulating number of studies have reported that CLIC1 is up-regulated in many tumor cells, such as hepatocellular carcinoma [10], gallbladder carcinoma [11], gastric can- cer [12], colon cancer [13], nasopharyngeal carcinoma [21], and breast cancer [22], and plays important roles in tumor progression by modifying cell cycle, apoptosis, cell adhesion, and promoting tumor metastasis. For ex- ample, Chen et al. [12] found that the high levels of CLIC1 expression in gastric cancer significantly Table 3 Cox multivariate analysis Parameter Age Gender WHO grade KPS Extent of resection Type of adjuvant treatment CCL20 expression Risk ratio 0.89 1.02 6.97 1.99 1.29 1.37 4.66 95% confidence interval 0.58–1.65 0.66–1.83 2.12–12.46 1.28–2.95 0.89–2.13 1.02–2.24 2.31–10.29 P 0.71 0.33 0.008 0.06 0.11 0.11 0.01 correlated with lymph node metastasis, lymphatic vessels and surrounding tissues infiltration, pathological staging, and survival time of patients; Wang et al. [23] shown that CLIC1 expression in lung adenocarcinoma was positively correlated with the T staging of the tumor and was negatively correlated with the shorter postoperative survival time of patients; Similarly, overexpression of CLIC1 was detected in gallbladder carcinoma and also found to significantly increase cell motility and invasion of the poorly metastatic gallbladder carcinoma cell line [11]. These results strongly imply that CLIC1 plays an important role in tumor advancement. However, its con- nection with human glioma has remained unknown. Our current study provided the evidence in support of such a connection using a cohort of 128 archived clinical glioma specimens. We first detected high expression of CLIC1 in glioma tissues compared with non-neoplastic brain tissues. Further support for a possible role of CLIC1 in glioma pathogenesis derived from the analysis that revealed a strong correlation of CLIC1 expression with the histopathological staging and inversely, with the survival of the disease. These findings are consistent with the previous reports which indicated that overex- pression of CLIC1 is a potential prognostic marker for hepatocellular carcinoma [9], gallbladder carcinoma [10], gastric cancer [11], and lung adenocarcinoma [23]. In summary, our data provide the first evidence that CLIC1 expression might play an important role in the regu- lation of aggressiveness in human gliomas. The elevated ex- pression of CLIC1 might represent a valuable prognostic marker for this disease. This study adds to the current