PXD068597-1

PXD068597 is an original dataset announced via ProteomeXchange.

Title	Aging in pancreatic ductal adenocarcinoma
Description	Aging is a critical yet understudied determinant in pancreatic ductal adenocarcinoma (PDAC). Despite a strong epidemiological association with age, conventional PDAC preclinical models fail to capture the histopathological and stromal complexities that emerge in older organisms. Using an age-relevant syngeneic orthotopic model, we demonstrate that organismal aging accelerates PDAC progression and metastasis. Through transcriptomic profiling, we identify a conserved extracellular matrix gene signature enriched in cancer-associated fibroblasts (CAFs) from aged tumors, consistent with an augmented fibrotic landscape that supports immunosuppression, metastatic tropism, and poor prognosis. To directly test the functional impact of stromal aging, we employed heterochronic co-implantation models, revealing that revitalizing the aged tumor stroma with young CAFs restores immune infiltration and attenuates metastasis in older hosts. Conversely, aged CAFs, while immunosuppressive, fail to enhance metastasis in young hosts, suggesting that a youthful microenvironment exerts dominant regulatory control over disease progression. These findings demonstrate that stromal age is a critical modulator of both immune exclusion and metastatic behavior in PDAC. Importantly, our work establishes a new conceptual framework for understanding how aging shapes the tumor microenvironment in PDAC and opens a fertile avenue of investigation into age-specific stromal regulation. Moreover, this work raises compelling questions about the underlying molecular mechanisms—questions now accessible through our model—and lays the foundation for future efforts to therapeutically target stromal aging in PDAC.
HostingRepository	PRIDE
AnnounceDate	2026-01-12
AnnouncementXML	Submission_2026-01-11_16:11:56.624.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weiliang Huang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-19 14:25:57	ID requested
⏵ 1	2026-01-11 16:11:57	announced

Gupta P, Murad R, Ling L, Zhang Y, Duong-Polk K, Huang W, Scortegagna M, Maganti S, Galapate CM, Commisso C, The Aging Microenvironment is a Determinant of Immune Exclusion and Metastatic Fate in Pancreatic Cancer. Cancer Res, ():(2025) [pubmed]

10.1158/0008-5472.can-25-1904;

submitter keyword: pancreatic ductal adenocarcinoma, cancer-associated fibroblasts,Aging, immunosuppression, metastasis

Weiliang Huang
contact affiliation	Sanford Burnham Prebys
contact email	whuang@sbpdiscovery.org
lab head
Weiliang Huang
contact affiliation	Sanford Burnham Prebys
contact email	whuang@sbpdiscovery.org
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/2026/01/PXD068597

PRIDE project URI

• PRIDE
  1. PXD068597
     1. Label: PRIDE project
     2. Name: Aging in pancreatic ductal adenocarcinoma