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Elevated levels of ...
Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer
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- Kerzeli, Iliana Kyriaki (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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- Kostakis, Alexandros (författare)
- Uppsala universitet,Institutionen för farmaci
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- Türker, Polat (författare)
- Uppsala universitet,Urologkirurgi
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- Malmström, Per-Uno (författare)
- Uppsala universitet,Urologkirurgi
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- Hemdan, Tammer, 1974- (författare)
- Uppsala universitet,Urologkirurgi
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- Mezheyeuski, Artur (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Vall dHebron Inst Oncol, Barcelona, Spain
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- Ward, Douglas G. (författare)
- Univ Birmingham, Inst Canc & Genom Sci, Coll Med & Dent Sci, Bladder Canc Res Ctr, Birmingham, England
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- Bryan, Richard T. (författare)
- Univ Birmingham, Inst Canc & Genom Sci, Coll Med & Dent Sci, Bladder Canc Res Ctr, Birmingham, England
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- Segersten, Ulrika (författare)
- Uppsala universitet,Urologkirurgi
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- Lord, Martin (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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- Mangsbo, Sara, 1981- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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(creator_code:org_t)
- BioMed Central (BMC), 2023
- 2023
- Engelska.
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Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 23:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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-naive 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 < 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.Conclusions The 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Nyckelord
- Biomarkers
- Matrix metalloproteinase 12 (MMP12)
- Urothelial bladder cancer
- Single-cell transcriptomics
- Proteomics
- Proximity Extension Assay (PEA)
- Macrophages
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Kerzeli, Iliana ...
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Kostakis, Alexan ...
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Türker, Polat
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Malmström, Per-U ...
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Hemdan, Tammer, ...
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Mezheyeuski, Art ...
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Ward, Douglas G.
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Bryan, Richard T ...
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Segersten, Ulrik ...
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Lord, Martin
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Mangsbo, Sara, 1 ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Urologi och njur ...
- Artiklar i publikationen
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BMC Cancer
- Av lärosätet
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Uppsala universitet