PXD060376

PXD060376 is an original dataset announced via ProteomeXchange.

Title	Rise in KRT17 sensitizes platinum-resistant ovarian cancer organoids to targeted therapies
Description	Variable responses to platinum chemotherapy and the development of resistant disease drive high mortality in high-grade serous ovarian cancer (HGSOC). Here, we developed the organoid drug resistance assay (ODR-test) to quantify the patient-specific efficacy of platinum treatment and generated post-platinum lines as an in vitro model of platinum-resistant ovarian cancer (PROC). We observed a gradual increase in resistance, mirroring the clinical outcomes of patients. Transcriptional and proteomic analyses of post-platinum phenotypes revealed changes in cell adhesion and differentiation as adaptive mechanisms irrespective of the basal resistance level. We found that Keratin 17 (KRT17) is a mediator of developing resistance and validated its function by CRISPR/Cas9 and overexpression. Additionally, we determined KRT17 (K-score) as a significant negative prognostic factor for survival based on analysis of a tumor microarray (N=377) of patients with advanced HGSOC. In organoids, increased KRT17 levels enhanced sensitivity to PI3K/Akt inhibitors Alpelisib and Afuresertib, highlighting the potential of KRT17 as a stratification biomarker for targeted therapies. These findings quantify patient-specific platinum response, identify PROC via KRT17 as a biomarker, and propose alternative targeted therapy for this challenging group of patients.
HostingRepository	PRIDE
AnnounceDate	2025-12-22
AnnouncementXML	Submission_2025-12-22_00:11:49.668.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ilaria Piga
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-30 11:20:20	ID requested
⏵ 1	2025-12-22 00:11:50	announced

10.1016/j.isci.2025.113999;

Reichenbach J, Schmid J, Hierlmayer S, Zhang T, Piga I, Geweniger S, Fischer J, Davesar A, Vasovic N, Chelariu-Raicu A, Kraus F, Burges A, Czogalla B, Mayr D, Straub T, Klein C, Olsen JV, Mahner S, Trillsch F, Kessler M, Organoid platinum-resistance model identifies KRT17 as a biomarker of targeted therapy in ovarian cancer. iScience, 28(12):113999(2025) [pubmed]

submitter keyword: None

Jesper Velgaard
contact affiliation	University of Copenhagen Faculty of Health and Medical Sciences Novo Nordisk Foundation Center for Protein Research Proteomics Program Copenhagen N Denmark
contact email	Jesper.Olsen@cpr.ku.dk
lab head
Ilaria Piga
contact affiliation	CPR
contact email	ilaria.piga@cpr.ku.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD060376

PRIDE project URI

• PRIDE
  1. PXD060376
     1. Label: PRIDE project
     2. Name: Rise in KRT17 sensitizes platinum-resistant ovarian cancer organoids to targeted therapies