Evaluation of hTERT, KRT7, and survivin in urine for noninvasive detection of bladder cancer using real-time PCR.

BACKGROUND: Transitional cell carcinoma (TCC) of the bladder is the second most common genitourinary malignancy. Because of the low sensitivity of urinary cytology and the invasiveness and expense of frequent cystoscopies for the detection of low-grade superficial lesions, we aim to establish a sensitive molecular approach to detect bladder cancer noninvasively. METHODS: Voided urine samples were collected from 80 patients with bladder cancer at the time of diagnosis, in addition to 30 patients with non-bladder cancer urological diseases and 20 healthy volunteers. The level of hTERT, KRT7, and survivin (SVV) mRNAs were analyzed using a qRT-PCR assay. RESULTS: The optimal threshold values for hTERT, KRT7, and SVV in urine were calculated by ROC curves analysis. The overall sensitivity was 81.3%, 91.3%, and 68.8% for hTERT, KRT7, and SVV, respectively, which were significantly higher than urine cytology (22.2%, p < 0.001). A higher positive ratio was obtained using multi-marker detection in comparison to single marker detection. The combined use of markers increased the sensitivity of cytology from 22.2 to 100%. In contrast with the urine cytology method, the sensitivity of these biomarkers was not correlated with the grades and stages of the bladder tumors. CONCLUSIONS: Our data indicate that urinary hTERT, KRT7, and SVV have superior sensitivities over cytology. The combined use of these markers offers a powerful potential assay and promising tool for a sensitive, noninvasive, and highly specific diagnostic method and follow-up of low-grade TCC of the bladder.

Diagnostic value of urinary survivin as a biomarker for bladder cancer: a systematic review and meta-analysis of published studies.

OBJECTIVE: This study is a meta-analysis and aims to determine the value of urinary survivin for detecting bladder cancer (BC) on the basis of preceding statistical performance and to compare their diagnostic value. MATERIALS AND METHODS: Considering that the urinary survivin data were from both RNA and protein levels, the key words "bladder cancer" AND "survivin" and "bladder cancer" AND "survivin RNA" were used; and PubMed, Web of Science, and Cochrane Library were systematically searched to identify relevant articles. The methodological quality of each study was assessed by QUADAS-2. Data were analyzed by STATA 12.0 and Meta-disc v.1.4 software package. A random-effects model was used and subgroup analysis was carried out to identify possible sources of heterogeneity. RESULTS: Nine articles for survivin protein test with 789 patients and 684 controls, and 12 articles for survivin RNA test with 880 patients and 922 controls were identified. The results showed that the pooled sensitivity was 0.79 (95% CI 0.73, 0.84), specificity was 0.87 (95% CI 0.79, 0.92) of the survivin protein test for bladder cancer, and the sensitivity and specificity was 0.84 (95% CI 0.79, 0.88) and 0.94 (95% CI 0.89, 0.97) of the survivin RNA test. The AUC of the two approaches was 0.89 (95% CI 0.86, 0.91) and 0.94 (95% CI 0.92, 0.96), respectively. CONCLUSIONS: The survivin protein and survivin RNA both had great potential as biomarkers for BC detection, and survivin RNA showed higher accuracy than survivin protein on BC diagnosis.

Performance of urinary survivin as a non-invasive molecular marker of bladdercarcinoma in a schistosomiasis endemic area.

OBJECTIVE: To compare the sensitivity, specificity, positive predictive value, negative predictive value of urinary survivin and that of urine cytology in the diagnosis of bladder carcinoma in a schistosoma endemic area. DESIGN AND SETTING: This is a 12-month prospective study of patients with features of bladder carcinoma as study group and patients with other urologic conditions and healthy volunteers as control group. PARTICIPANTS: Patients with features of bladder carcinoma formed the study group, while patients with other urological conditions and healthy volunteers formed the control group. RESULTS: There were 52 patients in study group and 36 patients in control group. The mean ages of patients in the study and control groups were 47.17 ± 17.00 and 44.19 ± 18.89 years respectively. There were 48 males and 4 females in the study group, giving a male: female ratio of 12:1. Thirty-one (60 %) of the patients were farmers and 44 patients (85%) had history suggestive of schistosomiasis at childhood. The sensitivity of urine cytology and survivin in the study were 29.1% and 100.0% respectively. The specificity of urine cytology and survivin were 100.0% and 100.0% respectively (p= 0.05). The marker was associated with false positive (FP) results in patients with prostate cancer. CONCLUSION: Urinary survivin is highly sensitive, specific and predictive of bladder carcinoma in our environment. The marker is associated with false positive results in patients with prostate cancer. FUNDING: By authors.