A4e4179e-1381-42ed-8fd2-883dbf55c9a9 - samples
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ABSTRACT:
PROVIDER: EGAD00001006657 | EGA |
REPOSITORIES: EGA
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Project description:Gastroentero-pancreatic neuroendocrine neoplasm(GEP-NEN) is consisted of neuroendocrine tumor and neuroendocrine carcinoma, which is a lethal, but under-investigated disease owing to its rarity. We established an organoid library of GEP-NEN and added their comprehensive molecular characterization.
2020-12-21 | GSE142720 | GEO
Project description:SmallRNAs profile in 60 Neuroendocrine Neoplasms (NEN) and 3 sera derived from NEN patients
| PRJEB51922 | ENA
Project description:Background: Neuroendocrine neoplasms (NENs) are mutationally quiet, and epigenetic mechanisms drive their development and progression. We aim to comprehensively characterize the microRNA (miRNA) profile of NENs, and explore downstream targets and their epigenetic modulation. Material and Methods: In total, 84 cancer-related miRNAs were analyzed in 84 NEN samples from lung and gastroenteropancreatic GEP origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N=63) and methylomics (N=30) were performed to predict miRNA target genes, signaling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas (TCGA) cohorts and in NEN cell lines. Results: We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signaling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. Conclusion: In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patient.
2023-03-31 | GSE211483 | GEO
Project description:Background: Neuroendocrine neoplasms (NENs) are mutationally quiet, and epigenetic mechanisms drive their development and progression. We aim to comprehensively characterize the microRNA (miRNA) profile of NENs, and explore downstream targets and their epigenetic modulation. Material and Methods: In total, 84 cancer-related miRNAs were analyzed in 84 NEN samples from lung and gastroenteropancreatic GEP origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N=63) and methylomics (N=30) were performed to predict miRNA target genes, signaling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas (TCGA) cohorts and in NEN cell lines. Results: We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signaling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. Conclusion: In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patient.
2023-03-31 | GSE211482 | GEO
Project description:Background: Neuroendocrine neoplasms (NENs) are mutationally quiet, and epigenetic mechanisms drive their development and progression. We aim to comprehensively characterize the microRNA (miRNA) profile of NENs, and explore downstream targets and their epigenetic modulation. Material and Methods: In total, 84 cancer-related miRNAs were analyzed in 84 NEN samples from lung and gastroenteropancreatic GEP origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N=63) and methylomics (N=30) were performed to predict miRNA target genes, signaling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas (TCGA) cohorts and in NEN cell lines. Results: We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signaling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. Conclusion: In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patient.
2023-03-31 | GSE211485 | GEO
Project description:Purpose: Advanced high-grade gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) are highly aggressive and heterogeneous epithelial malignancies with poor clinical outcomes. No therapeutic predictive biomarkers exist and representative preclinical models to study their biology are missing. Patient-derived (PD) tumoroids may enable fast ex vivo pharmacotyping and provide subsidiary biological information for more personalized therapy strategies in individual patients. Experimental Design: PD tumoroids were established from rare biobanked surgical resections of advanced high-grade GEP-NEN patients. Using targeted in vitro pharmacotyping and next-generation sequencing of patient samples and matching PD tumoroids, we profiled individual patients and compared treatment-induced molecular stress response and in vitro drug sensitivity to the clinical therapy response. Results: We demonstrate high success rates in culturing PD tumoroids of high-grade GEP-NENs within clinically meaningful timespans. PD tumoroids recapitulate biological key features of high-grade GEP-NEN and mimic clinical response to cisplatin and temozolomide in vitro. Moreover, investigating treatment-induced molecular stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5A (KDM5A) and interferon-beta (IFNB1) as two vulnerabilities that act synergistically in combination with cisplatin and may present novel therapeutic options in high-grade GEP-NENs. Conclusion: Patient-derived tumoroids from high-grade GEP-NENs represent a relevant model to screen drug sensitivities of individual patients within clinically relevant timespans and provide novel functional insights into drug-induced stress responses. Clinical patient response to standard-of-care chemotherapeutics matches with drug sensitivities of PD tumoroids. Together, our findings provide a functional precision oncology approach for gathering patient-centered subsidiary treatment information that will potentially increase therapeutic opportunities in the framework of personalized medicine.
2024-03-01 | GSE213504 | GEO
Project description:Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms. We used quantitative global proteomic analysis on 40 PNENs to compliment paired transcriptome data.
2021-11-30 | PXD024175 | Pride
Project description:Bulk RNA sequencing was performed on intestinal and airway organoids. Also airway organoid derived air-liquid interface cultures were sequenced
2021-08-17 | GSE181514 | GEO
Project description:Neuroendocrine neoplasms of the gallbladder and liver occur rarely in dogs and humans. A recent reclassification of human neuroendocrine neoplasms by the World Health Organization has refined categorization of these tumors by morphology, replicative indices, and molecular signatures. In humans, these factors correlate with survival outcomes. Improved characterization of these tumors is needed in dogs to identify diagnostic biomarkers and determine therapeutic strategies. To achieve this objective, the proteome of 3 canine hepatobiliary neoplasms was compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Thirty-two upregulated and 121 downregulated differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasm samples. Among the upregulated proteins is galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression in humans. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia in human medicine. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
2023-03-11 | PXD028822 | Pride