(UroToday.com) Urothelial bladder cancer (UBC) is most-frequently diagnosed at the nonmuscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required.
In a cohort of 90 treatment-naïve UBC patients, they utilised immuno-oncology focused multiplexed Proximity Extension Assays (PEA) to analyse plasma (n=90) and urine (n=40) samples. Public single-cell and bulk RNA-sequencing data from patient tumour tissues and murine OH-BBN-induced UBCs were also explored.
According to PEA analyses, MMP7 (p=0.028) and CCL23 (p=0.03) were found in higher levels at plasma of MIBC patients compared to NMIBC. CD27 (p=0.044) and CD40 (p=0.04) were found in higher levels in the urine samples of NMIBC patients. Increased plasma levels of MMP-12 were correlated with a shorter survival (HZ=1.8, p<0.001, 95% CI:1.3-2.5) and was an independent prognostic marker (p<0.001). This finding was validated in an independent patient cohort. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12.
The local production, but systemic diffusion of MMP12, suggests that MMP12 could be an important biomarker to complement histopathology-based risk stratification. Additionally, it may represent a pharmacological target in urothelial bladder cancer.
Presented by: Iliana K Kerzeli, PhD Student, Uppsala University, Uppsala, Sweden
Written by: Stephen B. Williams, MD, MS, FACS, @SWilliams_MD on Twitter, Division of Urology, University of Texas Medical Branch, Galveston, TX; Department of Surgery, University of Texas Medical Branch, Galveston, TX during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain