Matrix Metalloproteinases and Pro-Inflammatory Cytokines in Bladder Cancer: Diagnostic and Prognostic Perspectives:...

Bladder cancer (BC) is one of the most commonly diagnosed cancers of the genitourinary system and ranks ninth in terms of incidence worldwide. Due to the varied clinical course of the disease and the frequent tendency for tumor recurrence, diagnostic studies are being conducted to find non-invasive and prognostic markers that could be helpful in diagnosing BC. The aim of this review was to present the current state of knowledge on the role of extracellular matrix metalloproteinases (MMPs) and pro-inflammatory cytokines in the pathogenesis of bladder cancer, as well as to assess their potential as biomarkers measured in body fluids. The study reviewed the literature published in English between 2012 and 2025. The studies included clinical and experimental research analysing the expression and activity of selected metalloproteinases, including MMP-2, MMP-9, MMP-7 and MMP-1, and pro-inflammatory cytokines such as interleukins (ILs): IL-6, IL-8, IL-17, and IFN-γ in serum, urine, and tumor tissues of patients with BC, using immunochemical methods and genetic analyses. The collected data indicate that MMPs play a key role in the degradation of the extracellular matrix, facilitating invasion, angiogenesis, and metastasis. Elevated concentrations of MMP-2 and MMP-9, especially in urine, correlate with the clinical stage and histopathological malignancy of the tumor. MMP-7 may be important in the early stages of carcinogenesis, while MMP-1 shows promising potential in multi-marker panels. At the same time, chronic inflammation and increased pro-inflammatory cytokine activity play a key role in modulating the tumor microenvironment. IL-6 and IL-8 have high diagnostic value in urine tests, with IL-6 also serving as a prognostic marker. IL-17 is associated with more aggressive forms of the disease, while IFN-γ may reflect the immune response to BC treatment. There is also evidence of positive feedback between cytokines and MMPs, which intensifies the process of tumor invasion and progression. Therefore, both extracellular matrix metalloproteinases and pro-inflammatory cytokines may be promising non-invasive biomarkers of bladder cancer. Their combined assessment can increase the diagnostic and prognostic value compared to the analysis of individual parameters. However, further multicentre prospective studies are needed for clinical validation and standardisation of the methods of determination.