We present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy.

DNA methylation patterns are associated with the development and prognosis of cancer. The aim of this study was to identify novel methylation markers for the prediction of patient outcomes using microarray analysis of DNA methylation and RNA expression patterns in samples from long-term follow-up patients with nonmuscle invasive bladder cancer (NMIBC). A total of 187 human bladder specimens were used for microarray array or pyrosequencing (PSQ) analyses: 6 normal controls (NC) and 181 NMIBC. Tumor-specific hypermethylated genes were selected from a data set comprising 24 matched microarray-based DNA methylation and gene expression profiles (6 controls and 18 NMIBC), and their clinical relevance was verified by quantitative PSQ analysis. The methylation status of Homeobox A9 (HOXA9), ISL LIM homeobox 1 (ISL1) and Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) was significantly associated with decreased gene expression levels and aggressive clinicopathological characteristics. Multivariate regression analyses showed that hypermethylation of these genes was an independent predictor of disease recurrence (HOXA9, ISL1 and ALDH1A3, either alone or in combination) and progression (ISL1 and ALDH1A3, either alone or in combination) (each p < 0.05). The results of this study suggest that these novel methylation markers are independent prognostic indicators in NMIBC patients, which may facilitate the assessment of disease recurrence and progression in NMIBC patients and inform clinical decision making regarding treatment.

Purpose: Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells.Experimental Design: Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out.Results: Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH.Conclusion: Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa. Clin Cancer Res; 17(13); 4523-30. Ó2011 AACR.

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PurposeThe purpose of this article is to report establishment of the 1st Web-based database (DB) system to collect renal cell carcinoma (RCC) data in Korea.Materials and MethodsThe new Web-based DB system was established to collect basic demographic and clinicopahtological characteristics of a large cohort of patients with RCC in Korea. Data from a total of 6,849 patients were collected from 8 tertiary care hospitals that agreed to participate in organizing the Korean Renal Cell Carcinoma (KORCC) study group as of 1 July 2015. Basic demographic and clinicopathological characteristics were collected. The data of patients who underwent surgical treatments were analyzed to characterize Korean RCC.ResultsWe established the 1st Web-based DB of Korean RCC, a database comprising renal mass management cases from multiple centers in Korea. The data of 5,281 patients who underwent surgical management (mean follow-up, 32 months) were analyzed. The most common symptom was incidentally detected renal mass (76.9%). Clinical T1a was the most common (54.3%) stage and mean tumor size was 4.8±4.2 cm. Radical nephrectomy accounted for 62.7% of cases and an open approach was used in 50.7% and 52.2% of radical and partial nephrectomies, respectively. The 5-year overall, cancer-specific and recurrence-free survival rates were 88.1%, 92.2%, and 88.0%, respectively.ConclusionsWe report the 1st establishment of a Web-based DB system to collect RCC data in Korea. This DB system will provide a solid basis for the characterization of Korean RCC.

Abbreviations & Acronyms BMI = body mass index Cr = creatinine cT1a = clinical T1a EBL = estimated blood loss eGFR = estimated glomerular filtration rate PN = partial nephrectomy pT3a = pathological T3a RCC = renal cell carcinoma RN = radical nephrectomy Objectives: To compare the recurrence-free survival of partial nephrectomy and radical nephrectomy in patients with non-metastatic pathological T3a renal cell carcinoma. Methods: We reviewed the records of 3567 patients who had undergone a nephrectomy for renal cell carcinoma at five institutions in Korea from January 2000 to December 2010. The clinical data of 45 patients with pathological T3a renal cell carcinoma in the partial nephrectomy group were compared with 298 patients with pathological T3a renal cell carcinoma in the radical nephrectomy group. The effects of surgical methods on recurrence-free survival were assessed by a multivariate Cox proportional hazard analysis. All comparisons were repeated in subgroup analysis on 63 clinical T1a patients with tumors ≤4 cm. Results: During a median 43-month follow-up period, disease recurrence occurred in two patients (4.4%) in the partial nephrectomy group, and 94 patients (31.5%) in the radical nephrectomy group. The results from a multivariate model showed that radical nephrectomy was a significant predictor of recurrence. However, in subgroup analysis that included 63 clinical T1a pathological T3a patients, the recurrence-free survival rates were not significantly different between the two cohorts. The renal function was significantly better preserved in the partial nephrectomy cohort than in the radical nephrectomy cohort. Conclusions: Partial nephrectomy provides similar recurrence-free survival outcomes compared with radical nephrectomy in patients with clinical T1a pathological T3a renal cell carcinoma. However, there seems to be a higher risk of recurrence for large pathological T3a tumors treated by radical nephrectomy compared with small tumors treated by partial nephrectomy. Thus, large tumors with the same pathological T3a renal cell carcinoma grade could have hidden aggressive features.

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Operative parameters for RAPN appear to be less affected by tumor complexity. Functional outcomes of RAPN were superior to those of LPN. Renal function recovered continuously during the 60-month follow-up period after partial nephrectomy.