While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer. We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression. We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.

Bladder cancer (BC) is a common cancer but diagnostic modalities, such as cystoscopy and urinary cytology, have limitations. Here, high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOFMS) was used to profile urine metabolites of 138 patients with BC and 121 control subjects (69 healthy people and 52 patients with hematuria due to non-malignant disease). Multivariate statistical analysis revealed that the cancer group could be clearly distinguished from the control groups on the basis of their metabolomic profiles, even when the hematuric control group was included. Patients with muscle-invasive BC could also be distinguished from patients with non-muscle-invasive BC on the basis of their metabolomic profiles. Successive analyses identified 12 differential metabolites that contributed to the distinction between the BC and control groups, and many of them turned out to be involved in glycolysis and betaoxidation. The association of these metabolites with cancer was corroborated by microarray results showing that carnitine transferase and pyruvate dehydrogenase complex expressions are significantly altered in cancer groups. In terms of clinical applicability, the differentiation model diagnosed BC with a sensitivity and specificity of 91.3% and 92.5%, respectively, and comparable results were obtained by receiver operating characteristic analysis (AUC = 0.937). Multivariate regression also suggested that the metabolic profile correlates with cancer-specific survival time. The excellent performance and simplicity of this metabolomics-based approach suggests that it has the potential to augment or even replace the current modalities for BC diagnosis.

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Yun SJ, et al. Korean J Urol. 2013 Oct;54(10):645-650. https://doi.org/10.4111/kju.2013.54.10.645

Recent studies have suggested an increased prevalence of urolithiasis and recurrence associated with obesity. We assessed the influence of obesity on stone risk factors as well as on stone recurrence. A database of patient history, body mass index, and serum and urine chemistry was analyzed for 704 consecutive stone formers (467 first time stone formers and 247 recurrent stone formers). Obesity was defined as body mass index greater than 25 kg/m(2). The effect of obesity on stone risk factors and recurrence were stratified according to stone episodes. Of these, 163 (23.2%) patients who had been followed for more than 36 months (median 54, range 5 to 148) were included in recurrence analysis. Obesity was significantly associated with stone episodes (p = 0.043). Obese stone formers excreted increased amounts of sodium, calcium, uric acid and citrate, while the urinary pH in a 24-hour urine sample was decreased compared to nonobese stone formers (p <0.05, respectively). Stone analysis revealed that uric acid stone was significantly more commonly found in the obese patients (p = 0.046). Multivariate Cox regression model stratified by stone episodes revealed that obesity (HR 2.572, 95% CI 1.376-4.807, p = 0.003) was the only strong predictor of stone recurrence in first time stone formers. No association between obesity and stone recurrence was detected in recurrent stone formers. Kaplan-Meier curves showed identical results. This study reveals that obesity is associated with metabolic alterations and urinary stone recurrence. Weight control may be considered one of the preventive modalities against recurrent stone formation, especially in first time stone formers.

Circulating cell‐free microRNAs (miRNAs) are potential cancer biomarkers. The aim of this study was to identify miRNAs that are differentially expressed between benign pleural effusion (BPE) and lung adenocarcinoma‐associated malignant pleural effusion (LA‐MPE). The expression level of cell‐free miRNA was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (ten BPEs and ten LA‐MPEs). Real‐time quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to validate the profiling results obtained for the discovery set and those obtained for a validation set comprising 42 BPEs and 45 LA‐MPEs. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the identified miRNAs and other common tumor markers, such as carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21‐1. Microarray profiling showed that miR‐198 was significantly downregulated in LA‐MPE compared with BPE (p = 0.002). The miRNA microarray analysis results were confirmed by qRT‐PCR (p < 0.001) using the validation set. The AUCs for miR‐198, CEA and CYFRA 21‐1 in the validation set were 0.887, 0.898 and 0.836, respectively. The diagnostic performance of miR‐198 was comparable with that of CEA, but better than that of CYFRA 21‐1. The AUC for all three markers combined was 0.926 (95% confidence interval, 0.843–0.973) with a sensitivity of 89.2% and a specificity of 85.0%. The present study suggests that cell‐free miR‐198 from patients with pleural effusion might have diagnostic potential for differentiating LA‐MPE from BPE.