Tumor microbiome contributes to an aggressive phenotype in the basal-like subtype of pancreatic cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA723013 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14275300_1.fastq.gz | Fastqsanger.gz | |||
| SRR14275300_2.fastq.gz | Fastqsanger.gz | |||
| SRR14275301_1.fastq.gz | Fastqsanger.gz | |||
| SRR14275301_2.fastq.gz | Fastqsanger.gz | |||
| SRR14275302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 124 |
Similar Datasets
Project description:Despite the uniform mortality in pancreatic adenocarcinoma (PDAC), clinical disease heterogeneity exists with limited genomic differences. A highly aggressive tumor subtype termed basal-like was identified to show worse outcomes and higher inflammatory responses. Here, we focus on the microbial effect in PDAC progression and present a comprehensive analysis of the tumor microbiome in different PDAC subtypes. Tumors from 62 resectable PDAC patients were subjected to metagenomic sequencing and RNA-seq.
2021-08-30 | GSE172356 | GEO
Project description:Pancreatic cancer is a heterogenous disease and consists of distinct subtypes. Here, we searched for candidate driver genes of the basal-like/squamous subtype, a more aggressive molecular subtype of pancreatic ductal adenocarcinoma (PDAC). Through an integrated transcriptome analysis, we identified the serine/cysteine protease inhibitor, SERPINB3 (squamous cell carcinoma antigen 1, SCCA1), as being upregulated in the basal-like/squamous PDAC using a discovery and validation approach. SERPINB3 upregulation associated with decreased patient survival and a transcriptome profile indicative of the basal-like/squamous subtype. The goal of this study was aimed to identify SERPINB3 induced molecular signatures in PDAC.
2023-10-12 | GSE224564 | GEO
Project description:Pancreatic cancer is a heterogenous disease and consists of distinct subtypes. Here, we searched for candidate driver genes of the basal-like/squamous subtype, a more aggressive molecular subtype of pancreatic ductal adenocarcinoma (PDAC). Through an integrated transcriptome analysis, we identified the serine/cysteine protease inhibitor, SERPINB3 (squamous cell carcinoma antigen 1, SCCA1), as being upregulated in the basal-like/squamous PDAC using a discovery and validation approach. SERPINB3 upregulation associated with decreased patient survival and a transcriptome profile indicative of the basal-like/squamous subtype. The goal of this study was aimed to identify SERPINB3 induced molecular signatures in PDAC.
2023-10-12 | GSE223908 | GEO
Project description:Pancreatic cancer is a heterogenous disease and consists of distinct subtypes. Here, we searched for candidate driver genes of the basal-like/squamous subtype, a more aggressive molecular subtype of pancreatic ductal adenocarcinoma (PDAC). Through an integrated transcriptome analysis, we identified the serine/cysteine protease inhibitor, SERPINB3 (squamous cell carcinoma antigen 1, SCCA1), as being upregulated in the basal-like/squamous PDAC using a discovery and validation approach. SERPINB3 upregulation associated with decreased patient survival and a transcriptome profile indicative of the basal-like/squamous subtype. The goal of this study was aimed to identify SERPINB3 induced molecular signatures in PDAC.
2023-10-12 | GSE223536 | GEO
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:Breast cancer is a heterogeneous disease comprised of at least five major subtypes. Luminal subtype tumors confer a more favourable patient prognosis, which is in part, attributed to the Estrogen Receptor-alpha (ER) positivity and anti-hormone responsiveness of these tumors. Expression of the forkhead box transcription factor, FOXA1, also correlates with the luminal subtype and patient survival, but is present in a subset of ER-negative tumors. Similarly, FOXA1 is consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, basal breast cancer cell lines do not express FOXA1, and loss of FOXA1 in luminal cells increases migration and invasion, characteristics of the basal subtype. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favourable prognosis, we performed cDNA microarray analyses on luminal FOXA1-positive, ER-positive (MCF7, T47D) and FOXA1-positive, ER-negative (MDA-MB-453, SKBR3) cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal-signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Use of Gene Set Enrichment Analyses (GSEA) as a phenotyping tool revealed that FOXA1 silencing resulted in a transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to both luminal and basal genes within luminal breast cancer cells, suggesting that it not only transactivates luminal genes, but also represses basal-associated genes. From these results we conclude that FOXA1 controls plasticity between basal and luminal cells, playing a dominant role in repressing the basal phenotype, and thus tumor aggressiveness, in luminal breast cancer cells. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward a more aggressive cancer. FOXA1 siRNA treated breast cell lines compared directly to nonspecific siRNA treated cell lines using Agilent 4X44 microarrays.
2012-03-09 | E-GEOD-31003 | biostudies-arrayexpress
Project description:Despite the uniform mortality in pancreatic adenocarcinoma (PDAC), clinical disease heterogeneity exists with limited genomic differences. A highly aggressive tumor subtype termed 'basal-like' was identified to show worse outcomes and higher inflammatory responses. Here, we focus on the microbial effect in PDAC progression and present a comprehensive analysis of the tumor microbiome in different PDAC subtypes with resectable tumors using metagenomic sequencing. We found distinctive microbial communities in basal-like tumors and identified an increasing abundance of Acinetobacter, Pseudomonas and Sphingopyxis to be highly associated with carcinogenesis. Functional characterization of microbial genes suggested the potential to induce pathogen-related inflammation. Host-microbiota interplay analysis provided new insights into the tumorigenic role of specific microbiome compositions and demonstrated the influence of host genetics in shaping the tumor microbiome. Taken together, these findings indicated that the tumor microbiome is closely related to PDAC oncogenesis and the induction of inflammation. Additionally, our data revealed the microbial basis of PDAC heterogeneity and proved the predictive value of the microbiome, which will contribute to the intervention and treatment of disease.
| S-EPMC8408135 | biostudies-literature
Project description:SERPINB3 induces the aggressive basal-like/squamous subtype and promotes invasion and metastasis in pancreatic cancer
| PRJNA928787 | ENA
Project description:Gata2 deficiency delays leukemogenesis while contributes to aggressive leukemia phenotype in Cbfb-MYH11 knockin mice
| PRJNA535600 | ENA
Project description:Breast cancer is a heterogeneous disease comprised of at least five major subtypes. Luminal subtype tumors confer a more favorable patient prognosis, which is in part, attributed to the Estrogen Receptor-α (ER) positivity and anti-hormone responsiveness of these tumors. Expression of the forkhead box transcription factor, FOXA1, also correlates with the luminal subtype and patient survival, but is present in a subset of ER-negative tumors. Similarly, FOXA1 is consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, basal breast cancer cell lines do not express FOXA1, and loss of FOXA1 in luminal cells increases migration and invasion, characteristics of the basal subtype. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favorable prognosis, we performed cDNA microarray analyses on luminal FOXA1-positive, ER-positive (MCF7, T47D) and FOXA1-positive, ER-negative (MDA-MB-453, SKBR3) cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal-signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Use of Gene Set Enrichment Analyses (GSEA) as a phenotyping tool revealed that FOXA1 silencing resulted in a transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to both luminal and basal genes within luminal breast cancer cells, suggesting that it not only transactivates luminal genes, but also represses basal-associated genes. From these results we conclude that FOXA1 controls plasticity between basal and luminal cells, playing a dominant role in repressing the basal phenotype, and thus tumor aggressiveness, in luminal breast cancer cells. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward a more aggressive cancer.
2012-03-09 | GSE31003 | GEO