Whole genome bisulfite sequencing identifies stage- and subtype-specific DNA methylation signatures in pancreatic cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1018862 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26107700_1.fastq.gz | Fastqsanger.gz | |||
| SRR26107700_2.fastq.gz | Fastqsanger.gz | |||
| SRR26107701_1.fastq.gz | Fastqsanger.gz | |||
| SRR26107701_2.fastq.gz | Fastqsanger.gz | |||
| SRR26107702_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 94 |
Similar Datasets
Project description:In pancreatic ductal adenocarcinoma (PDAC), no recurrent metastasis-specific mutation has been found, suggesting that epigenetic mechanisms, such as DNA methylation, are the major contributors of late-stage disease progression. Here, we performed the first whole genome bisulfite sequencing (WGBS) on mouse and human PDAC organoid models to identify stage-specific and subtype-specific DNA methylation signatures in PDAC. With this approach, we identified thousands of DMRs that can distinguish between the stages and subtypes of PDAC. Stage-specific DMRs are associated with genes related to nervous system development and cell-cell adhesions and are enriched in promoters and bivalent enhancers. Subtype-specific DMRs showed hypermethylation of GATA6 transcriptional networks in the squamous subtype and hypermethylation of EMT transcriptional networks in the progenitor subtype. These results indicate that aberrant DNA methylation contributes to both PDAC progression and subtype differentiation, resulting in significant and reoccurring DNA methylation patterns with diagnostic and prognostic potential.
2024-01-29 | GSE243528 | GEO
Project description:In pancreatic ductal adenocarcinoma (PDAC), no recurrent metastasis-specific mutation has been found, suggesting that epigenetic mechanisms, such as DNA methylation, are the major contributors of late-stage disease progression. Here, we performed the first whole-genome bisulfite sequencing (WGBS) on mouse and human PDAC organoid models to identify stage-specific and molecular subtype-specific DNA methylation signatures. With this approach, we identified thousands of differentially methylated regions (DMRs) that can distinguish between the stages and molecular subtypes of PDAC. Stage-specific DMRs are associated with genes related to nervous system development and cell-cell adhesions, and are enriched in promoters and bivalent enhancers. Subtype-specific DMRs showed hypermethylation of GATA6 foregut endoderm transcriptional networks in the squamous subtype and hypermethylation of EMT transcriptional networks in the progenitor subtype. These results indicate that aberrant DNA methylation contributes to both PDAC progression and subtype differentiation, resulting in significant and reoccurring DNA methylation patterns with diagnostic and prognostic potential.
| S-EPMC10963232 | biostudies-literature
Project description:Frontotemporal dementia is characterized by progressive atrophy of frontal and/or temporal cortices and an early age of onset. The disorder is highly heterogenic, comprising several genetic causes as well as a diverse phenotypic landscape of sporadic cases. Here we investigated the proteomic signatures of human brain frontal and temporal cortical lobes to identify key pathways involved in the three most frequent genetic subtypes of frontotemporal dementia. We included 38 patients with either an autosomal dominant repeat expansion in the C9ORF72 gene (n = 16), or a mutation in the GRN gene (n = 9) or the MAPT gene (n = 13), and 11 non-demented controls. Using data-independent quantitative proteomic analysis on laser-dissected tissues we identified brain region-specific protein signatures for these genetic frontotemporal dementia subtypes compared to non-demented controls. Using published single cell RNA expression data for cell type enrichment we deduced the involvement of major brain cell types in driving these different protein signatures. Using gene ontology analysis, we identified distinct genetic subtype- and cell type-specific biological processes. In the GRN-mediated subtype, we observed higher protein expression related to immune processes, with a role for endothelial cells and astrocytes, and lower protein expression implicating mitochondrial dysregulation, primarily in neurons. In the MAPT-mediated subtype, we observed higher protein expression associated with dysregulation of RNA processing in multiple cell types, and lower protein expression implicating altered neuronal functioning via dysregulation of oligodendrocytes. Comparison of the MAPT-mediated frontotemporal dementia signature with one obtained from Alzheimer’s disease brains demonstrated only partial overlap in protein dysregulation, thus separating general neurodegenerative processes and highlighting the frontotemporal dementia-specific involvement of altered RNA processing and oligodendrocyte dysfunction. Taken together, our results indicate a role for different brain cell types and biological mechanisms in frontotemporal dementia, revealing both genetic subtype-specific processes, and processes shared with other neurodegenerative diseases such as Alzheimer’s disease.
2023-03-10 | PXD022872 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by high heterogeneity, and the postoperative prognosis of different patients often varies greatly. Therefore, the classification of pancreatic cancer patients and precise treatment becomes particularly important. In this study, 1H NMR spectroscopy was used to analyze the 76 PDAC serum samples and identify the potential metabolic subtypes. The metabolic characteristics of each metabolic subtype were screened out and the relationship between metabolic subtype and the long-term prognosis was further identified. The clinical stages of PDAC did not show the metabolic differences at the serum metabolomic level. And three metabolic subtypes, basic, choline-like and amino acid-enriched types, were defined by the HCA of the serum metabolites and the disturbed metabolic pathways. The characteristic metabolites of each PDAC subtype were identified, and the metabolite model was established to distinguish the PDAC patients in the different subtypes. Among the three metabolic subtypes, choline-like type displayed better long-term prognosis compared with the other two types of patients. Metabolic subtypes are of clinical importance and can fully express the heterogeneity in the actual life activities of pancreatic cancer. The excavation of metabolic subtypes based on this will be more accurate and in line with clinical reality, so as to guide clinical precision individualization treatment.
2022-03-04 | ST002113 | MetabolomicsWorkbench
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
Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-05-29 | PXD006512 | Pride
Project description:Proteomic analyses identify dysregulated proteins and pathways between low-risk and high-risk subtype of early-stage lung adenocarcinoma and their prognostic impacts.Sample labels: A,low-risk tumor;B,low-risk normal;C,high-risk tumor;D,high-risk normal.
2020-07-18 | MSV000085775 | MassIVE
Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-03-01 | PXD008373 | Pride
Project description:BackgroundHair follicles (HFs), upon development, undergo repetitive cycles of growth (anagen), regression (catagen), and rest (telogen). The transition between the stages is determined by multiple molecular signals, including DNA methylation, which plays important roles in mammalian cellular identity and is essential for the development of HFs. Secondary hair follicles (SHFs) in cashmere goat exhibit classic cyclic hair development, and little has been done on a genome-wide scale to examine potentially methylated genes involved in the hair cyclic transition.ResultsGenome-wide DNA methylation profiles between skin tissues sampled during the anagen and telogen stages in cashmere goats were investigated using whole-genome bisulfite sequencing (WGBS). The methylation status was observed to be higher in the skin samples with HFs in the telogen than those in the anagen stage. A total of 1311 differentially methylated regions (DMRs) were identified between the two groups, which contained 493 fully annotated DMR-related genes (DMGs) (269 Hyper- DMGs and 224 Hypo-DMGs). Furthermore, a significant over-representation of the functional categories for DMGs related to immune response and intercellular crosstalk during hair cycling was observed. By integrating DNA methylation and mRNA expression data, we revealed that four genes (FMN1, PCOLCE, SPTLC3, and COL5A1) are crucial factors for elucidating epigenetic mechanisms contributing to the telogen-to-anagen transition.ConclusionOur study provided systematic methylome maps pertaining to the hair cycling stages (anagen vs telogen) at a single-base resolution, and revealed stage-specific methylation loci during cashmere growth or quiescence. Furthermore, we identified epigenetically regulated genes that are potentially involved in HF development and growth in cashmere goats, and likely in other mammal species.
| S-EPMC6114738 | biostudies-literature
Project description:Research of lncRNA expression signatures for four molecular subtype of breast cancer
| PRJNA779793 | ENA