{"entity": "publication", "iuid": "ff2c40df55e34e3baf4877363a35b322", "timestamp": "2026-06-07T08:44:18.299Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ff2c40df55e34e3baf4877363a35b322.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ff2c40df55e34e3baf4877363a35b322"}}, "title": "Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer.", "authors": [{"family": "Kerzeli", "given": "Iliana K", "initials": "IK"}, {"family": "Kostakis", "given": "Alexandros", "initials": "A"}, {"family": "T\u00fcrker", "given": "Polat", "initials": "P"}, {"family": "Malmstr\u00f6m", "given": "Per-Uno", "initials": "PU"}, {"family": "Hemdan", "given": "Tammer", "initials": "T"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Ward", "given": "Douglas G", "initials": "DG"}, {"family": "Bryan", "given": "Richard T", "initials": "RT"}, {"family": "Segersten", "given": "Ulrika", "initials": "U"}, {"family": "Lord", "given": "Martin", "initials": "M"}, {"family": "Mangsbo", "given": "Sara M", "initials": "SM"}], "type": "journal article", "published": "2023-06-30", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "23", "issue": "1", "pages": "605", "issn-l": "1471-2407"}, "abstract": "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.\n\nIn 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-na\u00efve 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.\n\nPlasma 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.\n\nThe 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.", "doi": "10.1186/s12885-023-11100-0", "pmid": "37391708", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10311740"}, {"db": "pii", "key": "10.1186/s12885-023-11100-0"}], "notes": [], "created": "2023-11-29T19:27:10.569Z", "modified": "2023-11-29T19:27:10.572Z"}