HepaCAM Expression And Its Clinical Significance In Clear Cell Renal Cell Carcinoma And Association Between HOGG1Gene Polymorphism And The Risk Of Bladder Cancer: A Meta-annlysis

Background:Hepatocyte cell adhesion molecule (hepaCAM) is a new member of immunoglobulin superfamily (IgSF), which has the capacibility of suppressing the proliferation of tumor cells. HepaCAM is supposed to be a new tumor suppressor gene (TSG). HepaCAM has been verified to be in close relationship with various human tumors, including bladder cancer and breast cancer.Objective:1. To evaluate expression of HepaCAM in renal clear cell carcinoma,and to delineate the relativity between HepaCAM expression and the occurrance of CCRCC.2. To investigate expression of HepaCAM in CCRCC, and to explore the relativity between HepaCAM expression and the progression of CCRCC.Methods:Paraffin-embedded tissue sections from73patients with CCRCC and12CCRCC adjacent renal tissues were included in the study. Among these objects,50patients are male,23are female;25patients are elder than60,48are younger than60;17patients have the tumors larger than7cm in diameter,56smaller than7cm in diameter. According to the pathologic stage method of American Joint Committee on Cancer2002(AJCC-2002), there are52objects in T1stage,14in T2stage,7in T3stage,2in N2stage. According to the TNM stage method, there are52patients in Ⅰ stage,12in Ⅱ stage,7in Ⅲstage, and2in Ⅳ stage. The non-biotin immunohistochemical method was adopted to analyze the expression of HepaCAM in all85samples. Image-ProPlus6.0software was employed to estimate the Integrated Optical Density (IOD) of the immunohistochemical image, and the correlation of IOD and clinical features of CCRCC was analyzed. SPSS13.0software was used for statistical analysis.Results:HepaCAM expression was downregulated in CCRCC, while upregulated in CCRCC adjacent tissues. The IOD in the two groups was8203.87±8431.88and36639.28±20851.94, respectively. Compared with CCRCC adjacent group, HepaCAM expression was significantly lower in CCRCC group (P<0.05). Expression of HepaCAM had no relations with clinical features such as gender, age, tumor size, T stage and TNM stage (all P>0.05).Conclusions:1. HepaCAM expression is lower in CCRCC compared with CCRCC adjacent tissues. This study indicates that HepaCAM is supposed to act as a marker for carcinogenisis of kidney.2. HepaCAM expression is lower in CCRCC, but not correlative to the clinical characters such as age, sex, tumor size, T stage and TNM stage and so on.3. HepaCAM expression is lower in CCRCC compared with CCRCC adjacent tissues. The study could pave a new approach or target therapy of CCRCC Objective:8-hygroxyguanine is an important product during the oxidate injury of DNA, which may be a vital molecule to switch on canceration. hOGG1plays a significant role in clearing8-hygroxyguanine. Therefore, hOGG1Ser326Cys Polymorphism has been reported to contribute to the risk of various cancers, including bladder cancer. However, the conclusions were controversy. To determine whether there is a significant association of hOGG1Ser326Cys polymorphism with the susceptibility of bladder cancer, we perform a comprehensive meta-analysis in this study.Methods:In this study, we conducted a systematic article search. The electronic Pubmed, Medline, and the Springer database were searched for publicatons on the association between hOGG1Ser326Cys polymorphism and bladder cancer through May20,2011, using phrases such as "human8-oxoguanineDNAglycosylase/hOGG1/GG1/OGG","polymorphism/genetic variation","bladder cancer/bladder carcinoma" and their combinations. We also searched relative articles in Chinese National Knowledge Infrastructure(CNKI) and China Biological Medical Literature Database(CBM) by May20,2011using the same words. All articles on the association of hOGGl Ser326Cys polymorphism and the risk of bladder cancer were found without any restrict on language. We screened the seeking articles according to inclusion criteria. Only studies which could provide detailed frequency of genotype were included in this meta-analysis. And characters of the individual articles was extracted by two independent author. Then, the following analyses were conducted using the Review Manager version4.2provided by Cochrane net. We chose random-effect model to pool the statistics if there are heterogenity between studies(Pheterogenity<0.10), otherwise fixed-effect model was applied(Pheterogenity>0.10). Odds Ratio(OR) and95%Confidential Interval(95%CI) were calculated. And P value<0.05was considered to be statistically significant. Meanwhile, we did the sensitivity test by including and excluding studies not in Hardy-Weinberg Equilibrium(HWE) to examing the stabilization of the meta-analysis. Funnel plot was also drafted to estimate the publication bias and egger test was calculated to test the symmetry of funnel plot by using Stata software version7.0.Results:Finally, seven case-control studies were identified, including2474cases and2408controls. Among all studies, three involved Asian populations, four involved Caucasian population, two invovled population-based studies, and five were hospital-based studies. In the seven final studies, six studies provided the data of diagnosted histology type of cancer. All studies, but two, were consistent with Hardy-Weinberg equilibrium.Overall, no significant associations were found between hOGG1Ser326Cys polymorphism and bladder cancer in codominant models:(GG vs. CC:OR=1.11,95%CI=0.74-1.66, P=0.63; GC vs CC:OR=1.07,95%CI=0.80-1.41, P=0.65). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs GC+CC:OR=1.05,95%CI=0.65-1.70, P=0.85), dominant model (GG+GC vs CC:OR=1.07,95%CI=0.87-1.32, P=0.53) and allele model (G vs C:OR=1.06,95%CI=0.90-1.26, P=0.49).In Caucasian population, no significant associations were found between hOGG1Ser326Cys polymorphism and bladder cancer in codominant models:(GG vs. CC: OR=0.87,95%CI=0.66-1.16, P=0.35; GC vs CC:OR=1.07,95%CI=0.67-1.71, P=0.78). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs GC+CC:OR=0.85,95%CI=0.65-1.12, P=0.25), dominant model (GG+GC vs CC:OR=0.85,95%CI=0.74-1.47, P=0.82) and allele model (G vs C:OR=0.95,95%CI=0.85-1.06,P=0.38).In Asian population, also no significant associations were found between hOGG1Ser326Cys polymorphism and bladder cancer in codominant models:(GG vs. CC: OR=1.34,95%CI=0.64-2.83, P=0.44; GC vs CC:OR=1.24,95%CI=0.77-2.02, P=0.37). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs GC+CC:OR=1.26,95%CI=0.50-3.17, P=0.62), dominant model (GG+GC vs CC:OR=1.16,95%CI=0.91-1.47, P=0.23) and allele model (G vs C:OR=1.14,95%CI=0.90-1.26, P=0.49).In transitional cell carcinoma of bladder, still no significant associations were found between hOGG1Ser326Cys polymorphism and bladder cancer in codominant models:(GG vs. CC:OR=1.21,95%CI=0.75-1.94, P=0.43; GC vs CC:OR1.11,95%CI=0.77-1.62, P=0.57). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs GC+CC:OR=1.12,95%CI=0.63-1.99, P=0.71), dominant model (GG+GC vs CC:OR=1.13,95%CI=0.87-1.48, P=0.35) and allele model (G vs C:OR=1.11,95%CI=0.91-1.35, P=0.32).In the stratified analyses by control sources, still, no significant associations were observed(all P>0.05).Excluding the studies not in HWE, the results were not significantly altered. hOGG1gene Ser326Cys polymorphism may be not correlative to the bladder cancer susceptibility (all P>0.05). The consequences indicated that the results of the meta-analysis were credible.Funnel plots were sysmetric, and egger test verified that there were no publication bias(P>0.05).Conclusions:1. The overall current literature on hOGG1Ser326Cys polymorphism and the risk of bladder cancer suggests no statistically significant association between the two.2. In the meta-analyses of studies conforming to HWE, the results shows lack of association between hOGG1Ser326Cys polymorphism and bladder cancer suceptibility(all P>0.05).3. In Caucasian and Asian population, hOGG1Ser326Cys polymorphism is not correlative with the risk of bladder cancer(all P>0.05).4. And hOGG1Ser326Cys Polymorphism does not contribute to the occurrence of transitonal cell carcinoma of bladder(all P>0.05).5. Additional primary studies may be necessary to provide evidence of any significant association between this specific polymorphism and bladder cancer. Objective To detect expression of HepaCAM in clear cell renal cell carcinoma (CCRCC), and to study the relativity between HepaCAM expression and the development of CCRCC.Methods Paraffin-embedded tissue sections from73patients with CCRCC and12CCRCC adjacent renal tissues were included in the study. The immunohistochemical(PV-9001) method was adopted to analyze the expression of HepaCAM in all samples. Image-ProPlus6.0software was employed to estimate the Integrated Optical Density (IOD) of the immunohistochemical image, and the correlation of IOD and clinical features of CCRCC was analyzed. SPSS13.0software was used to perform statistical analysis.Results HepaCAM expression was downregulated in CCRCC, while upregulated in CCRCC adjacent tissues. The IOD in the two groups was8203.87±8431.88and36639.28±20851.94, respectively. Compared with CCRCC adjacent group, HepaCAM expression was significantly lower in CCRCC group(P<0.05). Expression of HepaCAM had no relations with clinical features such as gender, age, tumor size, T stage and TNM stage.Conclusions HepaCAM expression is lower in CCRCC compared with CCRCC adjacent tissues, and may have a close relation to the development of CCRCC. This study indicate that HepaCAM is supposed to act as a marker for carcinogenesis of renal. Objective HOGG1Ser326Cys Polymorphism has been reported to contribute to the risk of bladder cancer in some but not all studies. To determine whether there is a significant association of hOGG1Ser326Cys polymorphism with the susceptibility of bladder cancer, we perform a comprehensive meta-analysis in this study.Methods The electronic Pubmed, Medline, and the Springer database were searched for publicatons of the association between hOGGl Ser326Cys polymorphism and bladder cancer through May20,2011. Seven case-control studies were identified, including2474cases and2408controls. From these identified publications, crude odds ratios (ORs) and95%confidence intervals (CIs) were calculated to estimate the strength of association using fixed-or random-effects models. Two investigators each extracted data and conducted the analysis independently.Results Overall, no significant associations were found between hOGG1Ser326Cys polymorphism and bladder cancer in codominant models:(GG vs. CC:OR=1.11,95%CI=0.74-1.66, P=0.63; GC vs CC:OR=1.07,95%CI=0.80-1.41, P=0.65). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs GC+CC:OR=1.05,95%CI=0.65-1.70, P=0.85), dominant model (GG+GC vs CC:OR=1.07,95%CI=0.87-1.32, P=0.53) and allele model (G vs C:OR=1.06,95%CI=0.90-1.26, P=0.49). In the stratified analyses by ethnity, control sources, pathology, Hardy-Wenberg Equilibrium, still, no significant associations were observed.Conclusions The overall current literature on hOGG1Ser326Cys Polymorphism and the risk of bladder cancer suggests no statistically significant association between the two. Additional primary studies may be necessary to provide evidence of any significant association between this specific polymorphism and bladder cancer.