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

Abstract

Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin‐19 (CYFRA21‐1), nuclear matrix protein 22 (NMP‐22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21‐1, 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 COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21‐1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut‐off value of COL4A1 + COL13A1 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 BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. 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 BCa.

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

“…Substantial attention is paid to relative abundance of carcinoembryonic antigen (CEA, sensitivity 50-80%, specificity above 80%) in combination with serum amyloid A (SAA) (sensitivity of 100%, specificity 83-100%) and also carbohydrate antigens CA 19-9 (sensitivity of 47.8%, specificity 90.1%), CA 125 (sensitivity of 57.1%, specificity 92% among CEA-negative patients), CA 72-4 (sensitivity of 50%, specificity 86%), and protein CYFRA21-1 (sensitivity up to 18.2% and 42.3% in stages A and B according to the modified Dukes' classifications) [3][4][5][6][7][8][9][10]. Nevertheless, the specificity for CRC diagnosis is questionable, since their presence and alterations are likewise associated with the development of squamous cell and hepatocellular carcinoma, lung, and bladder cancer [11][12][13]. Additionally, case study reports mention these proteins with regard to the pathology of the liver, musculoskeletal system, organs of vision, and pneumonia [14][15][16].…”

Long term exposure to γ‑rays induces radioresistance and enhances the migration ability of bladder cancer cells

“…In 2017, 79,030 novel cases of BCa (60,490 male and 18,540 female) and 16,870 mortalities due to BCa (12,240 male and 4,630 female) in US were reported (1). Cytology and certain urine-based markers, including nuclear matrix protein 22 (2) and surviving (3,4), have roles in monitoring individuals at high risk of developing BCa. Additionally, recent research has demonstrated that cigarette smoking (5) and imbalances in sex hormones (6) may be potential risks for the development of BCa.…”

Rapid and quantitative detection of urinary Cyfra21-1 using fluorescent nanosphere-based immunochromatographic test strip for diagnosis and prognostic monitoring of bladder cancer

“…Cytokeratin 19 fragments (Cyfra21-1) is a soluble fragment of keratin CK19. Serum Cyfra21-1 is an effective diagnostic biomarker for cancers such as lung cancer and oral/oropharyngeal squamous cell carcinoma [10][11][12], and previous studies also confirmed that the diagnostic specificity and sensitivity of urinary Cyfra21-1 for bladder cancer were about 60-90% and 40-92%, respectively [8,[13][14][15][16]. Immunoassaybased techniques such as electro chemiluminescent immunoassay, enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay were most often used for urinary Cyfra21-1 detection [17][18][19].…”