An intronic polymorphism rs2237062 in the CXCL14 gene influences HBV-related HCC progression in Chinese population.
ABSTRACT CXCL14 (C-X-C motif chemokine ligand 14) is a conserved member of chemokine family and functions as a chemoattractant for multiplicate immunocytes. CXCL14 expression is constitutive in normal tissues, but absent in wide range of epithelial tumors. Many reports have claimed its important role in tumorigenesis and vascularization. An association between rs2237062 polymorphism and hepatocellular carcinoma (HCC) susceptibility was found in patients with chronic HCV infection in Japanese population. Here we analyzed, by using a polymerase chain reaction-ligation detection reaction (PCR-LDR), the polymorphism in 202 non-HCC patients with HBV infection, 361 HBV-related HCC patients and 407 healthy controls. The aim was to detect the possible association of this single-nucleotide polymorphism (SNP) with HBV-related HCC susceptibility and progression. However, no association was found between rs2237062 polymorphism and susceptibility to HBV infection or HBV-related HCC. Intriguingly, our stratification analysis revealed that HBV-related HCC patients in advanced phase (TNM-II-IV stage) had significantly higher C allele frequency at this polymorphism than patients at early stage (TNM-I stage) (33.5% vs. 25.7%), and its odds ratio reached 1.47 (95% CI 1.06-2.04, P = 0.021). These results suggest that the rs2237062 polymorphism in the CXCL14 gene might influence HBV-related HCC progression in Chinese population.
SourceAvailable from: Weilin Wang[Show abstract] [Hide abstract]
ABSTRACT: C-X-C motif chemokine ligand 14 (CXCL14) is a novel gene that is expressed in many normal cells but is absent from or expressed at very low levels in cancerous tissues such as head and neck squamous cell carcinoma (HNSCC), prostate cancer, and pancreatic cancer. However, the relationship between CXCL14 and hepatocellular carcinoma (HCC) remains unclear. Therefore, the exact function of CXCL14, which may modulate antitumor immune responses in certain cancers, was evaluated. CXCL14 was downregulated in HCC tissues compared to adjacent normal tissues. Moreover, overexpression of CXCL14 had an inhibitory effect on cell proliferation, induced apoptosis and inhibited the invasion of HCC cells in vitro. Upregulation of CXCL14 by lentivirus also significantly suppressed the growth of subcutaneous tumors in nude mice in vivo. We further demonstrated that the loss of CXCL14 expression was regulated by promoter hypermethylation. CXCL14 induced tumor cell apoptosis through both the mitochondrial and nuclear apoptosis pathways. CXCL14 suppressed tumor cell proliferation through regulation of the cell cycle by downregulation of cyclins and cyclin-dependent kinases. In conclusion, CXCL14 plays a pivotal role as a potential tumor suppressor in HCC. The re-expression or upregulation of this gene may provide a novel strategy in HCC therapy in the future.Cancer Science 11/2013; 104(11). DOI:10.1111/cas.12279 · 3.53 Impact Factor
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ABSTRACT: Objective-Our aim was to identify the role of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in atherogenesis and to study the relationships between CCL19, CCL21, and CCR7 gene variants and coronary artery disease in a Chinese Han population. Approach and Results-Immunohistochemical analysis of samples with atherosclerosis of various stages showed increased CCL19, CCL21, and CCR7 expression in atherosclerotic coronary plaques compared with nonatherosclerotic controls. Expression levels increased in positive correlation with coronary lesion stage. Cell adhesion assays confirmed that CCL19 promoted monocyte adhesion, which was induced by CCR7, to human umbilical vein endothelial cells, an effect partially antagonized by atorvastatin. After the human umbilical vein endothelial cells were treated with CCR7-neutralizing antibody, both CCL19- and CCL21-induced monocyte to human umbilical vein endothelial cell migration and CCL19-induced monocyte to human umbilical vein endothelial cell adhesion were abolished. The associations between genetic variants of CCL19, CCL21, CCR7, and coronary artery disease in a Chinese Han population were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The following single nucleotide polymorphisms were associated with coronary artery disease: CCL19 rs2227302, CCL21 rs2812377, and CCR7 rs588019. Individuals with the CCL19 rs2227302 T allele or CCL21 rs2812377 G allele had higher plasma CCL19 levels than those with C/C genotype and higher CCL21 levels than those with T/T genotype in both case and control subjects. Conclusion-CCL19/CCL21-CCR7 is a novel homeostatic chemokine system that modulates human monocyte adhesion and migration, promoting atherogenesis. It is associated with coronary artery disease risk in Chinese Han individuals. These data suggest that the CCL19/CCL21-CCR7 axis plays an important role in atherosclerosis progression.Arteriosclerosis Thrombosis and Vascular Biology 07/2014; 34(9). DOI:10.1161/ATVBAHA.113.303081 · 5.53 Impact Factor
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ABSTRACT: To explore the molecular mechanism of hepatitis B virus-related and hepatitis C virus-related hepatocellular carcinoma, samples from hepatitis B virus and hepatitis C virus infected patients and the normal were compared, respectively. In both experiments, genes with high value were selected based on a genome-wide relative significance and genome-wide global significance model. Co-expression network of the selected genes was constructed, and transcription factors in the network were identified. Molecular complex detection algorithm was used to obtain sub-networks. Based on the new model, the top 300 genes were selected. Co-expression network was constructed and transcription factors were identified. We obtained two common genes FCN2 and CXCL14, and two common transcription factors RFX5 and EZH2. In hepatitis B virus experiment, cluster 1 and 3 had the higher value. In cluster 1, ten of the 17 genes and one transcription factor were all reported associated with hepatocellular carcinoma. In cluster 3, transcription factor ESR1 was reported related with hepatocellular carcinoma. In hepatitis C virus experiment, the value of cluster 3 and 4 was higher. In cluster 3, nine genes were reported to play a key role in hepatocellular carcinoma. In cluster 4, there were 5 genes in the 34 genes. To compare the relevance of a node in holding together communicating nodes, centralities based analysis was performed and we obtained some genes with high stress value. The analysis above helped us to understand the pathogenesis of hepatitis B virus and hepatitis C virus associated hepatocellular carcinoma.International Journal of Clinical and Experimental Medicine 01/2014; 7(11):4038-50. · 1.42 Impact Factor