Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deciphering Fatty Acid Biosynthesis-Driven Molecular Subtypes in Pancreatic Ductal Adenocarcinoma with Prognostic Insights

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge due to its high heterogeneity and aggressiveness. Recognizing the urgency to delineate molecular subtypes, our study focused on the emerging field of lipid metabolism remodeling in PDAC, particularly exploring the prognostic potential and molecular classification associated with fatty acid biosynthesis. Here we identified a 7-gene signature associated with fatty acid biosynthesis-related genes (FRGs), providing a robust tool for survival prediction. The high- FRGs score group displayed a poorer prognosis, lower immune infiltration abundance, and a higher tumor mutational burden. Notably, ACSL5, a key gene in 7-gene signature panel was upregulated in PDAC. The biological function of ACSL5 were validated with in vitro assay. Finally, we unveiled that ACSL5 played a crucial role in pancreatic cancer progression, promoting tumor initiation, metastasis, and immune evasion.

ORGANISM(S): Mus musculus

PROVIDER: GSE253315 | GEO | 2024/01/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Integrated lipidomics and proteomics reveal cardiolipin remodelling by upregulation of HADHA and indirectly by ELOVL5 in pancreatic cancer stem cells

Project description:Pancreatic cancer stem cells (PCSCs) characterize the pancreatic ductal adenocarcinomas (PDAC) and play a key role in driving their poor outcomes and resistance to targeted therapies. Although advanced proteomics and lipidomics technology facilitates quantitation of intracellular proteins and lipids, little is known about the regulation of signalling and metabolic pathways in PCSCs. Here we shown that PCSCs, derived from different PDAC cell lines, have specific and common proteome and lipidome modulations. PCSCs displayed down-regulation of L-lactate dehydrogenase A chain (LDHA) and, more interestingly, upregulation of trifunctional enzyme subunit alpha (HADHA) which is involved in cardiolipin remodelling. The upregulated proteins of PCSCs were mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics revealed a general increase of FAs 18:1, 20:2, 20:3, and 20:4, which are products of the catalytic activity of fatty acid elongase-5 (ELOVL5) predicted as common active gene of PCSCs. Moreover, in accordance with HADHA upregulation, lipidomics also showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of fatty acid elongation and cardiolipin remodelling in PCSCs, which could therefore represent attractive targets to improve the therapeutic treatments of PDAC

2021-09-09 | PXD023069 | Pride

Clinical value of nine circulating miRNAs in prognosis and diagnosis of PDAC

Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. The miRNA has been emerged as promising cancer biomarkers for PDAC. Nowadays, have been identified several miRNAs in serum or plasma of PDAC patients. However, there are not many of common miRNAs between them, and not all the studies have compared the serum/ plasma expression with the corresponding miRNAs present in the pancreatic tumor tissue. Due to this and considering that PDAC is the seventh leading cause of cancer death in Mexico, we initially identified the miRNAs that are differentially expressed in tissue from PDAC patients residing in the Mexican Republic, to later find out which of these miRNAs are overexpressed in the serum of patients with this type of cancer. In this way, nine common miRNAs were identified in tissue and serum of PDAC patients, of which four of them (miRNAs 223-3p, miR 210-3p, miR100-5p and miR-221 3p) could be proposed as a signature for the diagnosis of PDAC with a sensitivity and specificity of 0.74 and 0.82 respectively for patients residing in the Mexican Republic. The 56 target mRNA of these 9 miRNAs were found to be mainly enriched in fatty acid oxidation, glucose homeostasis, amino acid transport organonitrogen compound catabolism. Finally, four of the target mRNA may serve as a prognostic marker for PDAC in tissue samples.

2020-12-12 | GSE163031 | GEO

H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma

Project description:Pancreatic ductal adenocarcinoma is one of the most intractable and devastating of all malignant tumors. Epigenetic modifications involving both DNA methylation and histone modification have a relationship between tumor initiation and progression. However, the contribution of histone variants in the PDAC is unknown. Here, we demonstrated that the histone variant H2A.Z is highly expressed in PDAC cell lines and PDAC patients and its overexpression correlated with poor prognosis. We found that the three-histone H2A.Z isoforms (H2A.Z.1, H2A.Z.2.1 and, H2A.Z.2.2), are highly expressed in PDAC cell lines and PDAC patients. Knockdown of three H2A.Z isoforms induces a senescent phenotype, cell cycle arrest in phase G2/M, increased cyclin-dependent kinase inhibitor CDKN2A/p16, SA-β-galactosidase activity and interleukin 8 production in PDAC. Transcriptome analysis of knockdown of the H2A.Z isoforms showed altered gene expression in the fatty acid biosynthesis. As well as in the genes that control the cell cycle and DNA damage repair. Furthermore, H2A.Z isoform deficiency, reduces the tumor size in a mouse xenograft model in vivo, and sensitizes PDAC cells to gemcitabine. These results make H2A.Z a potential candidate as a diagnostic biomarker and therapeutic target for PDAC

2019-04-03 | GSE129182 | GEO

The side population of human pancreatic cancer expresses cancer stem cell-associated genes

Project description:Purpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival. Experimental design: Side and main population (MP) cells were isolated from 11 human PDAC resection specimens using fluorescence-activated cell sorting (FACS) after Hoechst incubation. Total RNA was extracted for whole-genome analysis. A gene signature for the purified SP (pSP; depleted from immune/endothelial CD45+/CD31+ cells) was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analyses for disease-free and overall survival. Results: An SP was identified in all PDAC samples. Whole-genome expression profiling of pSP revealed upregulation of genes related to therapy-resistance and of CSC-associated genes and pathways. A pSP signature of 32 up- or downregulated genes was capable of discriminating SP from MP in an independent set of 10 PDAC samples, and some contributing genes had a prognostic value in a separate series of 78 patients who underwent surgery for PDAC. Conclusion: Pancreatic cancer contains an SP with chemo-resistant and CSC-associated molecular characteristics. Genes from a newly defined pSP gene signature are related to survival of patients who undergo surgical resection for pancreatic cancer, and might therefore represent potential therapeutic targets. Microarray analysis was performed on SP and MP samples from 11 different human PDAC samples.

2014-09-26 | E-GEOD-42404 | biostudies-arrayexpress

S. aureus gene expression following AFN-1252 treatment

Project description:AFN-1252 is an inhibitor of fatty acid biosynthesis. Gene expression profiles were generated by microarray analysis of S. aureus cells following treatment with AFN-1252, an inhibitor of fatty acid synthesis. Fatty acid biosynthesis in S. aureus was inhibited by AFN-1252 for 15 minutes, and RNA was extracted to look at the gobal gene expression.

2010-07-29 | E-GEOD-19400 | biostudies-arrayexpress

Disturbed Balance of Protein Phosphatase Type 2A (PP2A) is Driving Epithelial-to-Mesenchymal Transition in Human Pan-creatic Cancer Patients

Project description:The incidence for pancreatic ductal adenocarcinoma (PDAC) is rising which has a low survival rate. In cancer, Epithelial-to-Mesenchymal transition (EMT) contribute to an aggressive phenotype. Protein Phosphatase Type 2A (PP2A) are initially regarded as tumor suppressors, the connection with EMT in patients is uncertain. We investigated the relation of a ‘PP2A’ gene signature (en-compassing catalytic, structural and regulatory subunits; and endogenous PP2A inhibitors and activators) with EMT in PDAC patients. We could demonstrate a link between PDAC and EMT in four patient datasets using datamining, correlation study and gene set analysis. Furthermore, we identified a strong association of PP2A with EMT in advanced pancreatic cancer patients and in particular a significant upregulation of PP2A inhibitor genes in aggressive/EMT-high PDAC. In vitro, pharmacological inhibition of PP2A through Okadaic acid induced EMT in human pancreatic cells. Two different cell models were developed and their morphology, gene and protein expression determined. In the more advanced OA-induced EMT model (OA7G), statistical changes in proteins of natural PP2A-inhibitors was observed and this requires further investigations. Translationally, these observations indicate that PP2A could be a central factor in cancer and it is therefore attractive to test compounds that can target PP2A enzyme activity in PDAC.

2023-07-20 | PXD037976 | Pride

Gene expression analysis between the pancreatic tissues of Pdx1-cre;Kras LSL-G12D and Pdx-cre;KrasLSL-G12D;IKK2/beta F/F mice

Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation. Pancreatic tissue from 4 groups of mice were used in this project: (1) the pancreas normal appearance of Pdx1-cre;KrasLSL-G12D;IKK2/beta mice, (2) the normal pancreas of Pdx1-cre;KrasLSL-G12D mice, (3) the pancreatic lesion of pancreatic intraepithelial neoplasia (PanIN) of Pdx1-cre;KrasLSL-G12D mice, and (4) the pancreatic lesion of PDAC of Pdx1-cre;KrasLSL-G12D mice. Each group included three mice. RNA samples from mouse pancreas were hybridized on GeneChip Mouse Gene 1.0 ST arrays (Affymetrix). Group (1) and group (2) were compared, and group (2), group (3) and group (4) were compared.

2012-01-24 | E-GEOD-33322 | biostudies-arrayexpress

Expression data from advanced stage of murine pancreatic ductal adenocarcinoma (PDAC) and control pancreas

Project description:We used microarrays to detail the global gene expression signature of PDAC and to identify distinct up- and down-regulated transcripts in these tumors compared to control pancreas. We also established from this dataset the metabolic signature of PDAC in order to define new metabolic therapeutic target for pancreatic cancer. PDAC were removed at an advanced stage of tumorigenesis in 7 to 10-weeks old mice with Mixed genetic background : B6CBAF1 x C57BL/6 x 129/Sv x FVB/n. Apparent signs used to determined the time of sacrifice : weight loss, lower activity and dull coat.

2014-09-16 | E-GEOD-61412 | biostudies-arrayexpress

Gene expression analysis between the pancreatic tissues of Pdx1-cre;Kras LSL-G12D and Pdx-cre;KrasLSL-G12D;IKK2/beta F/F mice

2012-01-24 | GSE33322 | GEO

Expression data from advanced stage of murine pancreatic ductal adenocarcinoma (PDAC) and control pancreas

2014-09-16 | GSE61412 | GEO