AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study.

Objective: This study aimed to measure the AHNAK2 urinary levels in bladder cancer patients. Material and methods: This prospective case–control study enrolled 67 participants between January and March 2019 and were categorized into bladder cancer group (n = 37), with histologically proven bladder cancer, and control group (n = 30), with histologically verified benign lesions or with no bladder cancer indication during follow-up. Urine samples of 15 mL were collected in the mid-morning before cystoscopy/surgery and an enzyme-linked immunosorbent assay was performed as per the manufacturer’s protocol. Bladder malignancies were classified according to the World Health Organization Tumor Classification. Group’s associations were evaluated with the Student t-test, Spearman’s rank correlation, and Mann–Whitney U test, while receiver operating curve was plotted for assessing the test’s performance. Results: Mean age of the bladder cancer group was 66.41 years (standard deviation = 10.04, range = 43-82 years) and the control group was 59.67 years (standard deviation = 10.44, range = 38-77 years). All bladder cancers were of the urothelial histotype, with the following pT distribution: pTa/papillary urothelial neoplasm of low malignant potential (n = 19; 28.4%), Primary tumor (pT) in situ (n = 4; 6%), pT1 (n = 7; 10.4%), and pT≥2 (n = 7; 10.48%). Mean AHNAK2 levels were higher in bladder cancer patients 49.08 pg/mL (standard deviation = 114.91) compared to controls 5.28 pg/mL (standard deviation = 6.65), P < .05). Significant differences were noted between non-invasive bladder cancer (n = 23; mean = 7.14 pg/mL; standard deviation = 7.26) and invasive bladder cancer (n = 14; mean = 117.99 pg/mL; standard deviation = 168.08) and between non-muscle invasive bladder cancer (mean = 23.19 pg/mL; standard deviation = 66.93) and muscle-invasive bladder cancer (mean = 160.05 pg/mL; standard deviation = 199.65) (P < .001). The result of the assays was given as follows: sensitivity: 64.19%, specificity: 66.67%, positive predictive value: 22.07%, negative predictive value: 92.37%, area under curve: 0.695, and 95% CI: 0.57-0.82. Conclusion: AHNAK2 protein could be used as bladder cancer surveillance biomarker. The inclusion of AHNAK2 levels in stratification nomograms might reduce the number of unnecessary cystoscopies.