PXD052973

PXD052973 is an original dataset announced via ProteomeXchange.

Title	Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-ß1 signaling mechanism
Description	Background: Prostate cancer (PCa) is the second most common type of tumor diagnosed in men and the fifth leading cause of cancer-related death in male patients. The response of metastatic disease to standard treatment is heterogeneous. As for now, there is no curative treatment option available for metastatic PCa, and the clinical tests capable of predicting metastatic dissemination and metastatic response to the therapies are lacking. Our recent study identifies aldehyde dehydrogenases ALDH1A1 and ALDH1A3 as critical regulators of PCa metastases, but the exact mechanisms mediating the role of these proteins in PCa metastatic dissemination remain not fully understood. Thus, plasma-based biomarkers of the ALDH-driven metastatic mechanisms are also not available. Methods: Genetic silencing, gene overexpression, or treatment with different doses of the retinoic acid (RA) isomers, which are the products of ALDH catalytic activity, were used to modulate the interplay between retinoic acid receptors (RARs) and androgen receptor (AR). RNA sequencing (RNAseq), reporter assays, and chromatin immunoprecipitation (ChIP) analysis were employed to validate the role of RARs and AR in the regulation of the transforming growth factor-beta 1 (TGFB1) expression. Gene expression levels of ALDH1A1, ALDH1A3, and the matrix metalloproteinase 11 (MMP11) and their correlation with pathological parameters and clinical outcomes were analyzed by mining several publicly available patient datasets as well as our multi-center transcriptomic dataset from patients with high-risk and locally advanced PCa. The levels of MMP11 protein were analyzed by enzyme-linked immunosorbent assay (ELISA) in independent cohorts of plasma samples from patients with localized or metastatic PCa and healthy donors, while plasma proteome profiles were obtained for selected subsets of PCa patients. Results: We could show that ALDH1A1 and ALDH1A3 genes differently regulate TGFB1 expression in a RAR- and AR-dependent manner. We further observed that the TGF-ß1 pathway contributes to the regulation of the MMPs, including MMP11. We have confirmed the relevance of MMP11 as a promising clinical marker for PCa using several independent gene expression datasets. Further, we have validated plasma MMP11 levels as a prognostic biomarker in patients with metastatic PCa. Finally, we proposed a hypothetical ALDH1A1/MMP11-related plasma proteome-based prognostic signature.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_19:07:01.926.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monika Pietrowska
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-10 12:49:51	ID requested
⏵ 1	2025-05-06 19:07:02	announced

Gorodetska I, Lukiyanchuk V, Gawin M, Sliusar M, Linge A, Lohaus F, H, ö, lscher T, Erdmann K, Fuessel S, Borkowetz A, Wojakowska A, Fochtman D, Reardon M, Choudhury A, Antonelli Y, Leal-Ega, ñ, a A, K, ö, seer AS, Kahya U, P, ü, schel J, Petzold A, Klusa D, Peitzsch C, Kronstein-Wiedemann R, Tonn T, Marczak L, Thomas C, Wid, ł, ak P, Pietrowska M, Krause M, Dubrovska A, 1 signaling mechanism. J Exp Clin Cancer Res, 44(1):105(2025) [pubmed]

10.1186/s13046-025-03299-6;

submitter keyword: Liquid biopsy, ALDH1A1, TGF-ß1, MMP11,Prostate cancer, Metastasis

Monika Pietrowska
contact affiliation	Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
contact email	monika.pietrowska@gliwice.nio.gov.pl
lab head
Monika Pietrowska
contact affiliation	Maria Sklodowska-Curie National Research Institute of Oncology
contact email	monika.pietrowska@io.gliwice.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052973
     1. Label: PRIDE project
     2. Name: Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-ß1 signaling mechanism