Urinary cell-free nucleic acid IQGAP3: A new non-invasive diagnostic marker for bladder cancer

Background: There is growing interest in developing new non-invasive diagnostic tools for bladder cancer (BC) that have better sensitivity and specificity than cystoscopy and cytology. This study examined the value of urinary cell-free nucleic acid (NA) as a diagnostic marker for BC. Material and methods: A total of 81 patients (74 BC and 7 normal controls) were used for a tissue set, and 212 patients (92 BC and 120 normal controls) were used as a urine set. Expression of tissue mRNA and urinary cell-free NAs was then examined. Results: Four candidate genes were top-ranked in the tissue microarray. Expression levels of two of these (IQGAP3 and TOP2A) in BC tissue and urine samples from BC patients were significantly higher than those in samples from the control groups. Binary logistic regression analysis of cell-free NA levels in urine samples revealed that IQGAP3 was significantly associated with BC: PicoGreen-adjusted odds ratio (OR), 3.434; confidence interval (CI), 2.999-4.180; P < 0.001; RiboGreen-adjusted OR, 2.242; CI, 1.793-2.840; P < 0.001. Further analysis of IQGAP3 urinary cell-free NAs with respect to tumor invasiveness and grade also yielded a high AUC, suggesting that IQGAP3 can discriminate between BC patients and non-cancer patients with hematuria. Conclusions: Levels of IQGAP3 urinary cell-free NA in BC patients were significantly higher than those in normal controls or patients with hematuria. High levels of IQGAP3 urinary cell-free NA also reflected high expression in BC tissues. Therefore, IQGAP3 urinary cell-free NA may be a complementary diagnostic biomarker for BC.