Pancreatic cancer prognosis is predicted by chromatin accessibility (Quantseq)
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ABSTRACT:
PROVIDER: PRJNA511020 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pancreatic cancer prognosis is predicted by chromatin accessibility
| PRJNA511018 | 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:Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.
| S-EPMC8144607 | biostudies-literature
Project description:Analysis of Single Nuclear Chromatin Accessibility Demonstrates Unique Myeloid Populations Differentially Influence Prognosis in Human Pancreatic Ductal Adenocarcinoma
| PRJNA1010705 | ENA
Project description:Background & Aims: Loss of ataxia-telangiectasia mutated, occurring in patients with multiple primary malignancies, including pancreatic cancer, is associated with poor prognosis. This study investigated the detailed molecular mechanism through which ataxia-telangiectasia mutated expression affects the prognosis of pancreatic-cancer patients Methods: Ataxia-telangiectasia mutated and phosphorylated ataxia-telangiectasia mutated levels in pancreatic-cancer patients who underwent surgical resection were analyzed using immunohistochemistry staining. RNA sequencing was performed on ataxia-telangiectasia mutated-knockdown pancreatic-cancer cells to elucidate the mechanism underlying the involvement of ataxia-telangiectasia mutated in pancreatic cancer. Results: Immunohistochemical analysis showed that 15.3% and 27.8% of clinical samples had low levels of ataxia-telangiectasia mutated and phosphorylated ataxia-telangiectasia mutated, respectively. Low phosphorylated ataxia-telangiectasia mutated expression substantially reduced overall and disease-free survival in pancreatic-cancer patients. Loss of ataxia-telangiectasia mutated promoted MET and NTN1 over-expression via hypoxia-inducible factor-1α, thereby enhancing pancreatic-cancer cell proliferation and migration. Conclusions: These results demonstrate that the loss of ataxia-telangiectasia mutated activates downstream proto-oncogenes, inhibits apoptosis, and promotes tumor growth; moreover, loss of phosphorylated ataxia-telangiectasia mutated leads to poor prognosis in pancreatic-cancer patients. Thus, ataxia-telangiectasia mutated may serve as a potential molecular marker to monitor patient prognosis and as a potential target for pancreatic cancer therapy
2023-02-13 | GSE224882 | GEO