Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1205927 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide new insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage, HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome, and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair, and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses appear to contribute to long-term survival in HGSC. Methylation profiling was done on 58 high grade serous ovarian cancer samples, 53 of which were primary tumors and and 5 were relapse tumors. 73 primary tumors from GSE65820 were also used as part of the cohort.
2022-08-26 | GSE211686 | GEO
Project description:Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide new insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage, HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome, and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair, and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes, and differential immune responses appear to contribute to long-term survival in HGSC.
2022-08-26 | GSE211669 | GEO
Project description:In this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes The two cohorts we have are defined as short term survivors (STS) with median survival of >3 month and <1 year postsurgery, and long term survivors (LTS) with overall survival of >3 years postsurgery.
2016-11-18 | GSE89997 | GEO
Project description:Background and aim: Only 10% of pancreatic ductal adenocarcinoma (PDAC) patients survive longer than five years. Factors underlining long-term survivorship in PDAC are not well understood. Therefore, we aimed to identify the key players in the tumor immune microenvironment (TIME) associated with long-term survivorship in PDAC patients. Methods: The immune-related gene expression profiles of resected PDAC tumors of patients who survived and remained recurrence-free of disease for ≥36 months (long-term survivors, n=10) were compared to patients who had survived ≤6 months (short-term survivors, n=10) due to tumor recurrence. Validation was performed by the spatial protein expression profile of immune cells using the GeoMx™ Digital Spatial Profiler. An independent cohort of samples consisting of 12 long-term survivors and 10 short-term survivors, was used for additional validation. The independent validation was performed by combining qualitative immunohistochemistry and quantitative proteinexpression profiling. Results: B cells were found to be significantly increased in the TIME of longterm survivors by gene expression profiling (p=0.018). The high tumor infiltration of B cells was confirmed by spatial protein profiling in the discovery and the validation cohorts (p=0.002 and p=0.01, respectively). The higher number of infiltrated B cells was found mainly in the stromal compartments of PDAC samples and was exclusively found within tumor cells in long-term survivors. Conclusion: This is the first comprehensive study that connects the immune landscape of gene expression profiles and protein spatial infiltration with the survivorship of PDAC patients. We found a higher number and a specific location of B cells in TIME of long-term survivors which emphasizes the importance of B cells and B cell-based therapy for future personalized immunotherapy in PDAC patients.
2022-12-14 | GSE220929 | GEO
Project description:In the current work, we present the first proteogenomic dataset of GBM clinical samples to date. We have assembled a cohort of 87 GBM patients of varying survival rates and performed MS-based proteomics analysis as well as RNA-seq in order to identify the molecular differences associated with survival and examine the contribution of each layer to GBM landscape. We show that each layer alone only partially reflects patient survival, but RNA-protein integration identifies clear patterns of layer-specific and layer-common processes specifically contributing to either short-term or long-term survival of patients. Furthermore, we compare our data to published single-cell RNA-seq of GBM tumors and evaluate the RNA-protein variability within single-cell based tumor subpopulations. We found that while all signatures of the four subpopulations tend to have high RNA-protein correlation, each signature is associated differently with survival. Altogether, these results highlight the potential of proteogenomics to further stratify heterogeneity in GBM tumors and identify processes contributing to poorer survival.
2021-04-16 | PXD018024 | Pride
Project description:RNA-seq dataset of high-grade serous ovarian cancer (HGSC) tumours from long-term survivors performed as part of the Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) study.
The dataset includes fastq files from 56 HGSC tumours (53 primary tumours and 3 recurrent tumours) from 53 long-term survivor patients.
Libraries were generated using the Illumina Stranded mRNA Prep and 150 bp paired-end sequencing was performed to a minimum of 100 million reads on Illumina NovaSeq 6000 instruments.
| EGAD00001008537 | EGA
Project description:About 50% of resected pancreatic ductal adenocarcinoma (PDAC) recur within just one year following surgery. Prognostic molecular markers predicting rapid recurrence are currently unavailable. We hypothesized that epigenetic differences at the level of chromatin accessibility, potentially linked to distinct differentiation states, might distinguish rapidly recurrent from non-recurrent tumors. Therefore, we interrogated genome-wide chromatin accessibility using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) on EpCAM+ PDAC malignant cells sorted from a cohort of 54 treatment-naïve resected tumors, in hopes of defining a tumor-intrinsic chromatin signature associated with recurrence. We discovered a signature of ~1000 loci that were differentially accessible between recurrent (disease free survival (DFS) < 1 year) and non-recurrent patients (DFS > 1 year). Through transcription factor (TF) binding motif analysis using supervised learning, we identified candidate TFs whose accessible motifs were differentially associated with recurrence. Nuclear localization of two such TFs as selected by top hits, ZKSCAN1 and HNF1b, were assessed by both immunohistochemistry and immunofluorescence on the tissue microarrays (TMA) of 40 out of 54 patients. Nuclear staining of HNF1b was strong in the non-recurrent and weak or absent in the recurrent patients but ZKSCAN1 was not significantly associated with recurrence. In an independent TMA of PDAC cohort (n=97) preselected for 52 long (OS 6 years)- and 45 short (OS 6 months)- term survivors, the number of nuclear positive cells for HNF1b was 52-fold higher in the long-term compared to the short-term survivors and that for ZKSCAN1 was 5.3-fold higher in the short-term compared to the long-term survivors. Altogether, these results provide novel prognostic molecular markers of early recurrence in PDAC and also suggest that the global epigenetic landscape is a prognostic feature in this disease.
2021-03-31 | GSE124231 | GEO
Project description:About 50% of resected pancreatic ductal adenocarcinoma (PDAC) recur within just one year following surgery. Prognostic molecular markers predicting rapid recurrence are currently unavailable. We hypothesized that epigenetic differences at the level of chromatin accessibility, potentially linked to distinct differentiation states, might distinguish rapidly recurrent from non-recurrent tumors. Therefore, we interrogated genome-wide chromatin accessibility using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) on EpCAM+ PDAC malignant cells sorted from a cohort of 54 treatment-naïve resected tumors, in hopes of defining a tumor-intrinsic chromatin signature associated with recurrence. We discovered a signature of ~1000 loci that were differentially accessible between recurrent (disease free survival (DFS) < 1 year) and non-recurrent patients (DFS > 1 year). Through transcription factor (TF) binding motif analysis using supervised learning, we identified candidate TFs whose accessible motifs were differentially associated with recurrence. Nuclear localization of two such TFs as selected by top hits, ZKSCAN1 and HNF1b, were assessed by both immunohistochemistry and immunofluorescence on the tissue microarrays (TMA) of 40 out of 54 patients. Nuclear staining of HNF1b was strong in the non-recurrent and weak or absent in the recurrent patients but ZKSCAN1 was not significantly associated with recurrence. In an independent TMA of PDAC cohort (n=97) preselected for 52 long (OS 6 years)- and 45 short (OS 6 months)- term survivors, the number of nuclear positive cells for HNF1b was 52-fold higher in the long-term compared to the short-term survivors and that for ZKSCAN1 was 5.3-fold higher in the short-term compared to the long-term survivors. Altogether, these results provide novel prognostic molecular markers of early recurrence in PDAC and also suggest that the global epigenetic landscape is a prognostic feature in this disease.
2021-03-30 | GSE124230 | GEO
Project description:About 50% of resected pancreatic ductal adenocarcinoma (PDAC) recur within just one year following surgery. Prognostic molecular markers predicting rapid recurrence are currently unavailable. We hypothesized that epigenetic differences at the level of chromatin accessibility, potentially linked to distinct differentiation states, might distinguish rapidly recurrent from non-recurrent tumors. Therefore, we interrogated genome-wide chromatin accessibility using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) on EpCAM+ PDAC malignant cells sorted from a cohort of 54 treatment-naïve resected tumors, in hopes of defining a tumor-intrinsic chromatin signature associated with recurrence. We discovered a signature of ~1000 loci that were differentially accessible between recurrent (disease free survival (DFS) < 1 year) and non-recurrent patients (DFS > 1 year). Through transcription factor (TF) binding motif analysis using supervised learning, we identified candidate TFs whose accessible motifs were differentially associated with recurrence. Nuclear localization of two such TFs as selected by top hits, ZKSCAN1 and HNF1b, were assessed by both immunohistochemistry and immunofluorescence on the tissue microarrays (TMA) of 40 out of 54 patients. Nuclear staining of HNF1b was strong in the non-recurrent and weak or absent in the recurrent patients but ZKSCAN1 was not significantly associated with recurrence. In an independent TMA of PDAC cohort (n=97) preselected for 52 long (OS 6 years)- and 45 short (OS 6 months)- term survivors, the number of nuclear positive cells for HNF1b was 52-fold higher in the long-term compared to the short-term survivors and that for ZKSCAN1 was 5.3-fold higher in the short-term compared to the long-term survivors. Altogether, these results provide novel prognostic molecular markers of early recurrence in PDAC and also suggest that the global epigenetic landscape is a prognostic feature in this disease.
2021-03-30 | GSE124229 | GEO
Project description:High-grade serous ovarian carcinoma (HGSOC) is generally associated with a very dismal prognosis. Nevertheless, patients with similar clinicopathological characteristics can have markedly different clinical outcomes. Our aim was the identification of novel molecular determinants influencing survival. Gene expression profiles of 12 HGSOC long-term and 27 short-term survivors (training set) were generated by microarray, and a prognostic signature was identified and further evaluated on an independent extensive HGSOC dataset through a meta-analysis approach.
2019-11-14 | GSE131978 | GEO