Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatially resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma II

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) exhibits profound molecular heterogeneity and poor prognosis, necessitating novel tailored therapies. The basal and classical subtypes - driven by glycolysis versus lipid metabolism - have distinct prognostic implications. We mapped PDAC molecular subtype heterogeneity, capturing spatially-resolved gene expression signatures and generating a comprehensive high-resolution dataset of 42,035 spatial spots. Subtype assignments were validated via multiplex immunofluorescence and quantitative analyses in patient-derived organoids. Our analysis resolved cancer cell signatures, deconvoluted intra-tumoral heterogeneity, and delineated a classical-to-basal trajectory. We identified metabolically ‘hot’, high-grade tumor niches characterized by concurrent enrichment of glycolysis and lipogenesis across both subtypes, nominating them as subtype-agnostic therapeutic targets. Preclinical models demonstrated that despite the basal subtype’s glycolysis dependence, both classical and basal tumors are susceptible to glycolysis inhibition. This work challenges the dogma of subtype-specific therapeutic silos and demonstrates highly adaptable energetic niches as reservoirs to drive tumor progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309739 | GEO | 2026/04/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Spatially resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma.

Project description:Pancreatic ductal adenocarcinoma (PDAC) exhibits profound molecular heterogeneity and poor prognosis, necessitating novel tailored therapies. The basal and classical subtypes - driven by glycolysis versus lipid metabolism - have distinct prognostic implications. We mapped PDAC molecular subtype heterogeneity, capturing spatially-resolved gene expression signatures and generating a comprehensive high-resolution dataset of 42,035 spatial spots. Subtype assignments were validated via multiplex immunofluorescence and quantitative analyses in patient-derived organoids. Our analysis resolved cancer cell signatures, deconvoluted intra-tumoral heterogeneity, and delineated a classical-to-basal trajectory. We identified metabolically ‘hot’, high-grade tumor niches characterized by concurrent enrichment of glycolysis and lipogenesis across both subtypes, nominating them as subtype-agnostic therapeutic targets. Preclinical models demonstrated that despite the basal subtype’s glycolysis dependence, both classical and basal tumors are susceptible to glycolysis inhibition. This work challenges the dogma of subtype-specific therapeutic silos and demonstrates highly adaptable energetic niches as reservoirs to drive tumor progression.

2026-04-22 | GSE316631 | GEO

Spatially resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma

2026-04-22 | GSE309669 | GEO

ELAPOR1 induces the classical/progenitor subtype and contributes to reduced disease aggressiveness through metabolic reprogramming in pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts. Diminished ELAPOR1 expression was linked to high histological grade, advanced disease stage, the basal-like/squamous subtype, and reduced patient survival in PDAC. In vitro experiments demonstrated that ELAPOR1 transgene expression not only inhibited the migration and invasion of PDAC cells but also induced gene expression characteristics associated with the classical/progenitor subtype. Metabolome analysis of patient tumors and PDAC cells revealed a metabolic program associated with both upregulated ELAPOR1 and the classical/progenitor subtype, encompassing upregulated lipogenesis and downregulated amino acid metabolism. 1-Methylnicotinamide, a known oncometabolite derived from S-adenosylmethionine, was inversely associated with ELAPOR1 expression and promoted migration and invasion of PDAC cells in vitro. Taken together, our data suggest that enhanced ELAPOR1 expression promotes transcriptome and metabolome characteristics that are indicative of the classical/progenitor subtype, whereas its reduction associates with basal-like/squamous tumors with increased disease aggressiveness in PDAC patients. These findings position ELAPOR1 as a promising candidate for diagnostic and therapeutic targeting in PDAC.

2024-04-02 | MTBLS9418 | MetaboLights

Hnf4a regulated transcriptome in organoid cultures derived from murine pancreas where HNnf4a is deleted after tumor initiation. [organoid]

Project description:Pancreatic ductal adenocarcinoma is an aggressive disease with a dismal five-year survival of 5%. Gene expression profiling has been instrumental for subtype classification in cancer, highlighting fundamental differences in tumors at the molecular level. Over the last years, multiple genomics studies have led to the classification of PDAC into two major subtypes: classical and basal-type. The classical subtype expresses higher levels of endodermal lineage specifiers, including HNF4A, GATA6, FOXA2, FOXA3 than the basal-type. The basal-type confers a worse prognosis, raising the possibility that loss of these lineage specifiers might enhance the malignant potential of PDAC. We found that the lineage specifier HNF4a plays a key role in maintaining a transcriptional network that characterizes the classical subtype, restraining growth in different PDAC models. Additionally, we demonstrated that HNF4a controls PDAC cell identity and proliferation, and represses the expression of SIX family members, two mesodermal lineage specifiers highly expressed in basal-type.

2021-01-14 | GSE138142 | GEO

SIX1 and SIX4 double knockout transcriptome profiling in 2D cell lines derived from murine pancreatic tumors

Project description:Pancreatic ductal adenocarcinoma is aggressive disease with a dismal five-year survival of 5%. Gene expression profiling has been instrumental for subtype classification in cancer, highlighting fundamental differences in tumors at the molecular level. Over the last years, multiple genomics studies have led to the classification of PDAC into two major subtypes: classical and basal-type. The classical subtype expresses higher levels of endodermal lineage specifiers, including HNF4A, GATA6, FOXA2, FOXA3 than the basal-type. The basal-type confers a worse prognosis, raising the possibility that loss of these lineage specifiers might enhance the malignant potential of PDAC. We found that the lineage specifier HNF4a plays a key role in maintaining a transcriptional network that characterizes the classical subtype, restraining growth in different PDAC models. Additionally, we demonstrated that HNF4a controls PDAC cell identity and proliferation, and represses the expression of SIX family members, two mesodermal lineage specifiers highly expressed in basal-type.

2021-01-14 | GSE144750 | GEO

Hnf4a regulated transcriptome in murine PDAC autochthonous tumors [FFPE tumors]

2021-01-14 | GSE138144 | GEO

Hnf4a regulated transcriptome in 2D cell lines derived from murine pancreatic tumors [2D cell lines]

2021-01-14 | GSE138143 | GEO

Hnf4a chromatin interactions in PDAC [ChIP-seq]

2021-01-14 | GSE138452 | GEO

Changes in chromatin accessibility landscape induced by Hnf4a in PDAC [ATAC-seq]

2021-01-14 | GSE138451 | GEO

The RNA binding protein QKI guides a pro-mesenchymal splicing program driving a subtype switch and limiting outcome in pancreatic cancer [PANC-1 and HPAF-II]

Project description:Transcriptomic analyses have identified two molecular PDAC subtypes, one of which, namely basal-like subtype, is associated with chemoresistance and worse clinical outcomes. Splicing dysregulation is known to contribute to PDAC malignancy. Functional studies in PDAC cells lines identified the splicing factor QKI as a key determinant of a basal-like splicing signature associated with increased tumor aggressiveness. Our studies demonstrate that QKI represses splicing events associated with the classical subtype and improved clinical outcome, while promoting basal-like events associated with shorter survival.

2024-02-05 | GSE234737 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data