Cuiju Mo

Cell Surface Glycan Alterations in Epithelial Mesenchymal Transition Process of Huh7 Hepatocellular Carcinoma Cell

Background and Objective Due to recurrence and metastasis, the mortality of Hepatocellular carcinoma (HCC) is high. It is well known that the epithelial mesenchymal transition (EMT) and glycan of cell surface glycoproteins play pivotal roles in tumor metastasis. The goal of this study was to identify HCC metastasis related differential glycan pattern and their enzymatic basis using a HGF induced EMT model. Methodology HGF was used to induce HCC EMT model. Lectin microarray was used to detect the expression of cell surface glycan and the difference was validated by lectin blot and fluorescence cell lectin-immunochemistry. The mRNA expression levels of glycotransferases were determined by qRT-PCR. Results After HGF treatment, the Huh7 cell lost epithelial characteristics and obtained mesenchymal markers. These changes demonstrated that HGF could induce a typical cell model of EMT. Lectin microarray analysis identified a decreased affinity in seven lectins ACL, BPL, JAC, MPL, PHA-E, SNA, and SBA to the glycan of cell surface glycoproteins. This implied that glycan containing T/Tn-antigen, NA2 and bisecting GlcNAc, Siaα2-6Gal/GalNAc, terminal α or βGalNAc structures were reduced. The binding ability of thirteen lectins, AAL, LCA, LTL, ConA, NML, NPL, DBA, HAL, PTL II, WFL, ECL, GSL II and PHA-L to glycan were elevated, and a definite indication that glycan containing terminal αFuc and ± Sia-Le, core fucose, α-man, gal-β(α) GalNAc, β1,6 GlcNAc branching and tetraantennary complex oligosaccharides structures were increased. These results were further validated by lectin blot and fluorescence cell lectin-immunochemistry. Furthermore, the mRNA expression level of Mgat3 decreased while that of Mgat5, FucT8 and β3GalT5 increased. Therefore, cell surface glycan alterations in the EMT process may coincide with the expression of glycosyltransferase. Conclusions The findings of this study systematically clarify the alterations of cell surface glycan in cancer EMT, and may provide novel insight for HCC metastasis.

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

UNLABELLED The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36- 2.36, P=0.00; TT vs. TC/CC OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.

TP53 and MDM2 Gene Polymorphisms, Gene-Gene Interaction, and Hepatocellular Carcinoma Risk: Evidence from an Updated Meta-Analysis

Background The association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent. To clarify the effects of these polymorphisms on HCC risk, an updated meta-analysis of all available studies was conducted. Methods Eligible articles were identified by search of databases including PubMed, Cochrane Library, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to July 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results Finally, a total of 10 studies including 2,243 cases and 3,615 controls were available for MDM2 SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism. With respect to MDM2 SNP309 polymorphism, significantly increased HCC risk was found in the overall population. In subgroup analysis by ethnicity and hepatitis virus infection status, significantly increased HCC risk was found in Asians, Caucasians, Africans, and HCV positive patients. With respect to TP53 R72P polymorphism, no significant association with HCC risk was observed in the overall and subgroup analyses. In the MDM2 SNP309–TP53 R72P interaction analysis, we found that subjects with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype were associated with significantly increased risk of developing HCC as compared with the reference MDM2 309TT and TP53 Arg/Arg genotype. Conclusions We concluded that MDM2 SNP309 polymorphism may play an important role in the carcinogenesis of HCC. In addition, our findings further suggest that the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop HCC. Further large and well-designed studies are needed to confirm this association.

CYP2D6 phenotypes and Parkinson's disease risk: A meta-analysis

BACKGROUND CYP2D6 polymorphisms have been reported to be associated with Parkinsons disease (PD) susceptibility, but the results of these previous studies were inconsistent. OBJECTIVES To explore whether PD patients with CYP2D6 gene variation have different risk to PD to those with normal function of CYP2D6. METHODS Systematic review with meta-analysis of case-controlled studies on the association between CYP2D6 and PD risk was conducted. Studies published up to August 1, 2013 were identified by searching electronic databases PubMed and Embase. Odds ratios (ORs) together with their corresponding 95% confidence intervals (CIs) were used to estimated the association between CYP2D6 polymorphisms and PD risk in different phenotype models. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed. RESULTS A total of 3521 PD Patients and 4476 controls from 29 case-control studies were identified. Overall, a borderline significant influence of the CYP2D6 polymorphisms on PD risk was observed (OR: 1.07, 95%CI: 0.99-1.16, p=0.106). Significant association was found when comparisons were performed in different phenotypes in PM versus EM (OR=1.33, 95% CI=1.01-1.74, p=0.044) and PM versus IM+EM (OR=1.32, 95% CI=1.11-1.56, p=0.002). In subgroup analysis stratified by country, significant association was demonstrated in British but not in other white subjects. No significant association was detected in subgroup analysis according to the age of onset and the source of patients. CONCLUSION The present meta-analysis demonstrated that the poor metabolizer phenotype of CYP2D6 confers a significant genetic susceptibility to PD in Caucasians, especially in British white subjects.

CYP2D6*4 Allele Polymorphism Increases the Risk of Parkinson’s Disease: Evidence from Meta-Analysis

Background Many epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson’s disease (PD) susceptibility. However, the results remain controversial. Objectives To clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted. Methods A comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed. Results Twenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14–1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06–1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06–1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10–1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02–1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form. Conclusions We concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association.

MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility: evidence from a meta-analysis.

ObjectiveThe SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and endometrial cancer risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association.MethodsAll studies published up to August 2013 on the association between MDM2 SNP309 polymorphism and endometrial cancer risk were identified by searching electronic databases PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM). The association between the MDM2 SNP309 polymorphism and endometrial cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsEight case–control studies with 2069 endometrial cancer cases and 4546 controls were identified. Overall, significant increase of endometrial cancer risk was found when all studies were pooled in the meta-analysis (GG vs. TT: OR = 1.464, 95% CI 1.246–1.721, P < 0.001; GG vs. TG + TT: OR = 1.726, 95% CI 1.251–2.380, P = 0.001; GG + TG vs. TT: OR = 1.169, 95% CI 1.048–1.304, P = 0.005). In subgroup analysis by ethnicity and HWE in controls, significant increase of endometrial cancer risks were observed in Caucasians and studies consistent with HWE. In subgroup analysis according to study quality, significant associations were observed in both high quality studies and low quality studies.ConclusionsThis meta-analysis suggests that MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility, especially in Caucasian populations. Further large and well-designed studies are needed to confirm this association.

An Updated Meta-Analysis on the Association of MDM2 SNP309 Polymorphism with Colorectal Cancer Risk

Background The mouse double minute 2 (MDM2) gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk. Methods All studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results A total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055–1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106–1.404, P=0.000) and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037–1.311, P= 0.010). In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected. Conclusions The present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.

The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients

Interleukin-8 (IL-8) belongs to the superfamily of CXC chemokines, contributing to human cancer progression through potential mitogenic, angiogenic, and motogenic functions. We hypothesize that the functional polymorphism of IL-8 may influence the inflammatory process during pathological stage from hepatitis to hepatocellular carcinoma (HCC). Two polymorphisms in the IL-8 gene (-251A/T and +781C/T) were examined in 160 cases of chronic hepatitis B, 80 cases of hepatitis B virus (HBV)-related liver cirrhosis (LC), 150 cases of HBV-related HCC, and 150 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. In the LC group, the AA genotypes were associated with a significantly decreased risk of LC compared with the TT genotype (OR=0.14, 95% CI 0.02-0.87, p=0.035). The data also revealed that subjects with the A allele appeared to have lower susceptibility to LC than those with the T allele (OR=0.48, 95% CI 0.25-0.92, p=0.027). The +781C/T polymorphism of IL-8 was not found relevant to the liver diseases. This study indicated that the IL-8 gene -251 AA genotype might be a protect factor for LC.

Association of PvuII and XbaI polymorphisms in estrogen receptor alpha gene with the risk of hepatitis B virus infection in the Guangxi Zhuang population.

BACKGROUND AND OBJECTIVE Available evidence has suggested that estrogen receptor alpha (ESR1) is implicated in the pathogenic process of hepatitis B infection. Therefore, we evaluated the association of PvuII (rs2234693) and XbaI (rs9340799) in ESR1 and HBV infection in Guangxi Zhuang populations. METHODS A total of 389 subjects were divided into four groups: 112 patients with chronic hepatitis B (CHB), 65 patients with hepatitis B virus (HBV)-related liver cirrhosis (LC), 107 patients with HBV-related hepatocellular carcinoma (HCC), and 105 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect ESR1 gene PvuII and XbaI polymorphisms. RESULTS Compared with healthy controls, binary logistic regression analyses show that the CC genotype of PvuII was associated with a significantly increased susceptibility to CHB compared with the TT genotype (OR=1.760, 95% CI 1.316-2.831; p=0.044). The PvuII CC genotype was also associated with significantly increased risk of HBV-related LC (OR=1.921, 95% CI 1.342-2.478; p=0.043). Similarly, the subjects bearing the homozygous CC genotype of PvuII polymorphism also had more than a 1.7-fold increased risk for development of HCC (OR=1.748, 95% CI 1.313-2.787; p=0.010) compared with those bearing the TT genotype. Furthermore, the AC haplotype was associated with a significantly increased risk of HCC with an OR of 1.456 (p=0.003). In contrast, there were no significant differences in the genotype and allele of XbaI polymorphisms in the ESR1 gene between the groups of patients and healthy controls. In addition, ESR1 polymorphisms were not significantly associated with susceptibility to HBV-related HCC when using CHB and LC patients as references. CONCLUSION We conclude that the CC genotype of PvuII in ESR1 is associated with an increased risk of CHB, HBV-related LC and HCC in Guangxi Zhuang populations.

Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta-analysis

BackgroundReduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association.MethodsAll studies published up to January 2014 on the association between XPC polymorphisms and gastric cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between XPC polymorphisms and gastric cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsSix studies with 1,355 gastric cancer cases and 2,573 controls were finally included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not observe a significant association when all studies were pooled into the meta-analysis. When stratified by ethnicity, source of control, and study quality, statistical significant association was not detected in all subgroups. With respect to Ala499Val and PAT−/+polymorphisms, we also did not observe any significant association with gastric cancer risk in the pooled analysis.ConclusionsThis meta-analysis based on current evidences suggested that the XPC polymorphisms (Lys939Gln, Val499Arg, and PAT−/+) did not contribute to gastric cancer risk. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069