ArticleBMC cancer2023
Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer.
Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Identification and Characterisation of Canine Osteosarcoma Biomarkers and Therapeutic Targets.Cancers · 2026Article
- Matrix metalloproteinase-12 in arterial diseases: context-dependent mechanisms of vascular remodeling and therapeutic implications.Frontiers in cardiovascular medicine · 2026Review
- Integrated single-cell and bulk tissue analyses reveal distinct macrophage subtypes and a candidate prognostic signature in colorectal cancer: implications for tumor immune characterization.Frontiers in immunology · 2026Article
- Development and prospective validation of a multitarget urine RNA assay for noninvasive detection of urothelial carcinoma.iScience · 2025Article
- Serum multiomics prediction of prognosis and adverse reactions to concurrent chemoradiotherapy in patients with esophageal cancer.British journal of cancer · 2025Article
- S-acyl transferase ZDHHC13 modulates tumor microenvironment interactions to suppress metastasis in melanoma models.The Journal of clinical investigation · 2025Article
- Development and validation of an Immune-related Gene-based model for predicting prognosis and immunotherapy outcomes in hepatocellular carcinoma patients.Scientific reports · 2025Article
- ADAMDEC1 promotes the malignant progression of cholangiocarcinoma by regulating NF-κB signaling pathway.Scientific reports · 2025Article
- Review
- Causal effect of serum matrix metalloproteinase levels on venous thromboembolism: a Mendelian randomization study.Epidemiology and health · 2024Article
- Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.Cardiovascular diabetology · 2023Article
- Review
- Evaluation of salivary matrix metalloproteinase-12 levels in patients with oral lekoplakia and oral squamous cell carcinoma using enzyme-linked immunosorbent assay.Journal of oral and maxillofacial pathology : JOMFPArticle
- Single-cell RNA sequencing and spatial transcriptome analysis in bladder cancer: Current status and future perspectives.Bladder cancer (Amsterdam, Netherlands)Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundUrothelial 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.
methodsIn 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.
resultsPlasma 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 < 0.001) associated with shorter overall survival (HR = 1.8, p < 0.001, 95% CI:1.3-2.5); this finding was validated in an independent patient OLINK cohort, but could not be established using a transcriptomic microarray dataset. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12.
conclusionsThe measurable levels of tumour-localised, immune-cell-derived MMP12 in blood suggest MMP12 as an important biomarker that could complement histopathology-based risk stratification. As MMP12 stems from infiltrating immune cells rather than the tumor cells themselves, analyses performed on tissue biopsy material risk a biased selection of biomarkers produced by the tumour, while ignoring the surrounding microenvironment.
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