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

Selim Komina; Gordana Petrusevska; Rubens Jovanovic; Slavica Kostadinova Kunovska; Sotir Stavridis; Saso Dohcev; Skender Saidi; Sonja Topuzovska

doi:10.5152/tud.2022.22132

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

Turk J Urol. 2022 Nov;48(6):423-430. doi: 10.5152/tud.2022.22132.

Authors

Selim Komina¹, Gordana Petrusevska¹, Rubens Jovanovic¹, Slavica Kostadinova Kunovska¹, Sotir Stavridis², Saso Dohcev², Skender Saidi², Sonja Topuzovska³

Affiliations

¹ Ss. Cyril and Methodious University, Faculty of Medicine, Institute of Pathology, Skopje, North Macedonia.
² Ss. Cyril and Methodious University, Faculty of Medicine, University Urology Clinic, Skopje, North Macedonia.
³ Ss. Cyril and Methodious University, Faculty of Medicine, Institute of Medical and Experimental Biochemistry, Skopje, North Macedonia.

Abstract

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 can cer, and control group (n=30), with histologically verified benign lesions or with no bladder cancer indica tion during follow-up. Urine samples of 15 mL were collected in the mid-morning before cystoscopy/surger y 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 devia tion=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 devia tion=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.