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.