Urinary NDRG2 and MCM8 Gene Expression as New Noninvasive Biomarkers for Diagnosis and Differentiation between Muscle and Non-Muscle Invasive Bladder Cancer

Abstract

Objectives: Noninvasive diagnosis of cancer bladder remains a challenge. The study aimed to evaluate the urinary gene expression of NDRG-2 (N-Myc downstream-regulated gene2) and MCM8 (the mini chromosome maintenance proteins) genes and their importance as novel urinary biomarkers for bladder cancer. In addition, to assess their diagnostic value in comparison with voided urine cytology is the focus of this work. Methods: the study included twenty healthy controls and fifty patients with bladder cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and voided urine cytology (VUC) were performed to demonstrate the NDRG2 and MCM-8 gene expression levels in the urine of healthy controls and bladder cancer patients. Results: There was a statistically significant decrease in NDRG-2 gene expression in bladder cancer group (4.38±0.66) compared to the control group (8.29±1.67). Gene expression of MCM-8 showed a statistically significant increase in bladder cancer group (5.57±0.79) in comparison to control group (4.55±1.39) with a significant negative correlation (ρ= -0.77) between NDRG-2 expression levels and tumor grade in cancer group (p<0.001), and a positive significant correlation (ρ=0.453) between MCM-8 expression levels and tumor grade in cancer group (p=0.001). NDRG-2 had the highest ability to predict bladder carcinoma (AUC of 1.0). In addition, the most precise differentiation between non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) with AUC of 0.814. Conclusion: Expression of NDRG-2 and MCM-8 may be novel potential noninvasive biomarkers for diagnosis and prognosis of bladder cancer and a good tool for differentiation between NMIBC and MIBC with NDRG-2 is the most precise for diagnosis and differentiation over MCM-8, VUC and combined use of NDRG-2 and MCM-8.