1. Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer
- Author
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Iliana K. Kerzeli, Alexandros Kostakis, Polat Türker, Per-Uno Malmström, Tammer Hemdan, Artur Mezheyeuski, Douglas G. Ward, Richard T. Bryan, Ulrika Segersten, Martin Lord, and Sara M. Mangsbo
- Subjects
Biomarkers ,Matrix metalloproteinase 12 (MMP12) ,Urothelial bladder cancer ,Single-cell transcriptomics ,Proteomics ,Proximity Extension Assay (PEA) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required. Methods In this study, immuno-oncology focused, multiplexed proximity extension assays were utilised to analyse plasma (n = 90) and urine (n = 40) samples from 90 newly-diagnosed and treatment-naïve bladder cancer patients. Public single-cell RNA-sequencing and microarray data from patient tumour tissues and murine OH-BBN-induced urothelial carcinomas were also explored to further corroborate the proteomic findings. Results Plasma from muscle-invasive, urothelial bladder cancer patients displayed higher levels of MMP7 (p = 0.028) and CCL23 (p = 0.03) compared to NMIBC patients, whereas urine displayed higher levels of CD27 (p = 0.044) and CD40 (p = 0.04) in the NMIBC group by two-sided Wilcoxon rank-sum tests. Random forest survival and multivariable regression analyses identified increased MMP12 plasma levels as an independent marker (p
- Published
- 2023
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