Pancreatic cancer prognosis is predicted by chromatin accessibility
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ABSTRACT:
PROVIDER: PRJNA511018 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pancreatic cancer prognosis is predicted by chromatin accessibility (Quantseq)
| PRJNA511020 | ENA
Project description:Pancreatic cancer prognosis is predicted by chromatin accessibility (RNA-Seq)
| PRJNA511023 | ENA
Project description:Pancreatic cancer prognosis is predicted by chromatin accessibility (ATAC-Seq)
| PRJNA511022 | ENA
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: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:This SuperSeries is composed of the SubSeries listed below.
2021-03-31 | GSE124232 | GEO
Project description: Not available
| S-EPMC8144607 | biostudies-literature
Project description:Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover novel regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.
2022-02-23 | GSE194249 | GEO
Project description:Chromatin accessibility landscape of human pancreatic ductal adenocarcinoma (PDAC)
| PRJNA717821 | ENA