Diagnostic and prognostic role of urinary collagens in primary human bladder cancer

Collagen type 4 alpha 1 ( COL 4A1) and collagen type 13 alpha 1 ( COL 13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL 4A1 and COL 13A1 in voided urine and compared the observed values with those of fragments of cytokeratin‐19 ( CYFRA 21‐1), nuclear matrix protein 22 ( NMP ‐22), and voided urine cytology in bladder cancer ( BC a). We collected voided urine samples from 154 patients newly diagnosed with BC a, before surgery and from 61 control subjects. Protein levels of COL 4A1, COL 13A1, CYFRA 21‐1, and NMP ‐22 in urine supernatants were measured using enzyme‐linked immunosorbent assays. Diagnostic performance and optimal cut‐off values were determined by receiver operating characteristic analysis. Urine levels of COL 4A1, COL 13A1, the combined values of COL 4A1 and COL 13A1 ( COL 4A1 + COL 13A1), and CYFRA 21‐1 were significantly elevated in urine from patients with BC a compared to the controls. Among these biomarkers, the optimal cut‐off value of COL 4A1 + COL 13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low‐grade tumors, high‐grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non‐muscle invasive BC a samples after the initial transurethral surgery. A high urinary COL 4A1 + COL 13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL 4A1 and COL 13A1 could be a potential diagnostic and prognostic biomarker for BC a. This easy‐to‐use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non‐muscle invasive and muscle invasive BC a.