Comprehensive Analysis of the Prognostic Value of Circulating MMP-7 Levels in Urothelial Carcinoma: A Combined Cohort Analysis, Systematic Review, and Meta-Analysis

Abstract

Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls (p < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts (p = 0.006, p < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases.

Enzymes Dysregulation in Cancer: From Diagnosis to Therapeutical Approaches

“…Among the enzymes that play a key role in the proliferation and aggressiveness of malignant cells there are glycolytic enzymes like lactate dehydrogenase (LDH), caspases, cyclin-dependent kinases, redox–detox enzymes and NAD + -dependent enzymes [ 7 , 8 ]. In recent years, several enzymes emerged as potential biomarkers for the diagnosis or prognosis of several malignancies [ 9 , 10 , 11 , 12 , 13 , 14 ]. Moreover, the possibility of designing specific inhibitors has also opened the possibility of utilizing these biomarkers as therapeutic targets [ 15 , 16 , 17 , 18 ].…”