PurposeS100A8 is a member of the S100 protein family containing 2EF-hand calcium-binding motifs. S100 proteins are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. Altered expression of this protein is associated with various diseases and cancers. The present study aimed to evaluate whether S100A8 has prognostic value for non-muscle-invasive bladder cancer (NMIBC).Materials and MethodsA total of 103 primary NMIBC samples obtained by transurethral resection were evaluated. mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results were compared with clinico-pathological parameters. The Kaplan-Meier method was applied to plot the curves for progression-free survival. The multivariate Cox regression model was used to identify the independent prognostic factors for progression.ResultsmRNA expression levels of S100A8 were significantly related to the progression of NMIBC. Kaplan-Meier estimates demonstrated significant differences in tumor progression according to the level of S100A8 expression (log-rank test, p<0.001). The multivariate Cox regression model revealed that the S100A8 mRNA expression level (hazard ratio: 12.538; 95% confidence interval: 2.245-70.023, p=0.004) was an independent predictor for disease progression of NMIBC.ConclusionsExpression levels of S100A8 might be a useful prognostic marker for disease progression of NMIBC.

PurposeDNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumor initiation and progression. Differences in methylation patterns between neoplastic and normal cells can be used to detect the presence of cancer. The aim of the present study was to evaluate the usefulness of glutathione-S-transferase-Pi (GSTP1) hypermethylation in discriminating between normal and prostate cancer (PCa) cells and in predicting tumor characteristics by use of quantitative pyrosequencing analysis.Materials and MethodsA total of 100 human prostate tissues obtained from our institute were used in this study: 45 for benign prostatic hyperplasia (BPH) and 55 for PCa. The methylation level of GSTP1 was examined by a quantitative pyrosequencing analysis. The associations between GSTP1 methylation level and clinico-pathological parameter were also compared.ResultsThe level of GSTP1 methylation was significantly higher in PCa samples than in BPH samples (56.7±32.7% vs. 1.6±2.2%, p<0.001). The sensitivity and specificity of GSTP1 methylation status in discriminating between PCa and BPH reached 85.5% and 100%, respectively. Even after stratification by stage, Gleason score, and prostate-specific antigen (PSA) level, similar results were obtained. A positive correlation between GSTP1 methylation level and serum PSA level was observed (r=0.303, p=0.002). There were no associations between GSTP1 methylation level and age, Gleason score, and staging.ConclusionsOur study demonstrates that GSTP1 methylation is associated with the presence of PCa and PSA levels. This methylation marker is a potentially useful indicator for the detection and monitoring of PCa.

PurposeTo validate whether FAM70B, which was found in our micro-array profiling as a prognostic marker for cancer survival, could accurately predict prognosis in patients with muscle-invasive bladder cancer (MIBC).Materials and MethodsA total of 124 patients with MIBC were enrolled in this study. The FAM70B expression level was analyzed by real-time polymerase chain reaction by using RNA from tumor tissues. The prognostic effect of FAM70B was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model.ResultsKaplan-Meier estimates showed a significant difference in progression-free survival (log-rank test, p=0.011) and cancer-specific survival (log-rank test, p=0.017) according to FAM70B gene expression level. By multivariate Cox regression analysis, high FAM70B expression was predictive of cancer progression (hazard ratio [HR], 2.115, p=0.013) and cancer-specific death (HR, 1.925; p=0.033). In the subgroup analysis, high expression of FAM70B was associated with poor cancer-specific survival, progression-free survival, and overall survival in the patients who underwent cystectomy (log-rank test, p=0.013, p=0.036, p=0.005, respectively). In the chemotherapy group, FAM70B expression was associated with cancer-specific survival and progression-free survival (log-rank test, p=0.013, p=0.042, respectively). Moreover, high FAM70B expression was associated with shorter cancer-specific survival in localized or locally advanced tumor stages (log-rank test, p=0.016).ConclusionsWe confirmed the significance of FAM70B as a prognostic marker in a validation cohort. Therefore, we propose that the FAM70B gene could be used to more precisely predict cancer progression and cancer-specific death in patients with MIBC.

The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancer-specific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. Kaplan-Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan-Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein-coupled receptor 149 (GPR149), was significantly associated with shorter time-to-progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.

DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, an association between prostate cancer susceptibility candidate (PRAC) methylation and genitourinary cancer was proposed. The aim of the present study was to evaluate the association between PRAC methylation status and clinicopathological parameters and prognosis in long-term follow-up primary nonmuscle invasive bladder cancer (NMIBC). The clinical relevance of PRAC methylation was determined in 136 human bladder specimens (eight normal controls [NCs] and 128 primary NMIBCs) using quantitative pyrosequencing analysis. PRAC methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates revealed significant difference in tumor recurrence and progression according to PRAC methylation status (both p < 0.05). Multivariate Cox regression analysis revealed that the PRAC methylation status was a strong predictor of recurrence (hazard ratio [HR], 2.652; p = 0.012) and progression (HR, 9.531; p = 0.035) of NMIBC. Enhanced methylation status of PRAC was positively associated with a high rate of recurrence and progression in NMIBC patients, suggesting that PRAC methylation may be a promising prognostic marker of NMIBC.