BackgroundThere is growing interest in circulating nucleic acids as cancer detection biomarkers. Therefore, the aim of the present study was to identify a key urinary cell-free RNA marker that may assist in the diagnosis of BC.ResultsFive cell-free RNAs were selected as candidate cell-free RNAs from tissue microarray data. An area under the curve (AUC) cut-off value of 0.7 in receiver operating characteristic (ROC) curve analysis identified four urinary cell-free RNAs for further analysis (CDC20, ESM1, UBE2C, and CA9; AUC = 0.716, 0.704, 0.721, and 0.702, respectively). Binary logistic regression analysis revealed that high expression of UBE2C was significantly associated with BC (OR, 1.754; CI, 1.147–2.682; p = 0.010). Analysis of UBE2C expression in urine samples from BC patients and hematuria controls yielded an AUC of 0.839, with a sensitivity of 82.5% and a specificity of 76.2%. UBE2C levels was significantly increased in G2 and G3 tumors compared to normal controls (p <0.001, respectively).Materials and MethodsUrine samples from 212 BC patients and 106 normal controls (64 healthy individuals and 42 with hematuria) were examined. The candidate cell-free RNAs identified from tissue microarrays derived from BC and normal control tissues was then measured in the urine samples.ConclusionsThe levels of urinary UBE2C cell-free RNA were significantly higher in BC samples than in normal and hematuria control samples. The higher levels of urinary UBE2C cell-free RNA in BC might reflect high expression in BC tissues. Therefore, urinary UBE2C cell-free RNA may be a valuable diagnostic marker for BC.
PurposeTopoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC).Materials and MethodsTwo patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort 2 (83 BC patients, 54 nonmalignant hematuric patients, and 61 normal controls) provided urine samples. Real-time quantitative polymerase chain reaction was used to measure expression of TopoIIA mRNA in tissues and TopoIIA cell-free DNA in urine samples.ResultsThe results showed that expression of TopoIIA mRNA in BC tissues was significantly higher than that in noncancer control tissues (p<0.001). The expression of urinary TopoIIA cell-free DNA in BC patients was also significantly higher than that in noncancer patient controls and hematuria patients (p < 0.001 and p < 0.001, respectively). High expression of urinary TopoIIA cell-free DNA was also detected in muscle invasive bladder cancer (MIBC) when compared with nonmuscle invasive bladder cancer (NMIBC) (p=0.002). Receiver operating characteristics (ROC) curve analysis was performed to examine the sensitivity/specificity of urinary TopoIIA cell-free DNA for diagnosing BC, NMIBC, and MIBC. The areas under the ROC curve for BC, NMIBC, and MIBC were 0.741, 0.701, and 0.838, respectively.ConclusionsIn summary, the results of this study provide evidence that cell-free TopoIIA DNA may be a potential biomarker for BC.
PurposeThe deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC.Materials and MethodsThe expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model.ResultsDBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05).ConclusionsThe expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC.
The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.
Prostate stem cell antigen ( PSCA ) is a cell-membrane glycoprotein consisting of 123 amino acids and highly expressed in the prostate, but there have been few reports on the relationship between rs2294008 of PSCA and prostate cancer in the literature. Therefore, we evaluated the association between rs2294008 and the risk of prostate cancer. A total of 240 prostate cancer patients and 306 controls (patients with benign prostatic hyperplasia) were enrolled. Genotype analysis of rs2294008 of PSCA was performed using PCR. Logistic regression analysis was performed according to the genotype of PSCA rs2294008. We found that CT and TT genotypes were associated with an insignificant risk of prostate cancer compared with the CC genotype ( P = 0.627 and 0.397, respectively). In addition, there was no significant difference in rs2294008 according to clinicopathological parameters, such as age, Gleason score, prostate-specific antigen (PSA), stage, and metastasis in prostate cancer ( P >0.05 for each). Age, Gleason score, PSA, pathologic stage, and metastasis did not modify the association between PSCA and the risk of prostate cancer (each P >0.05 for each). Taken together, the genetic polymorphism of PSCA rs2294008 was not associated with the risk of prostate cancer. Our results suggest that rs2294008 may not play a role in prostate carcinogenesis.
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