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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [methylation]

ABSTRACT: Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [methylation]

PROVIDER: PRJNA870486 | ENA |

REPOSITORIES: ENA

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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias

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Project description:Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [miRNA]

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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [methylation]

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.

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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [miRNA]

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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-31 | GSE211486 | GEO

Exploring the Epigenome in Gastroenteropancreatic Neuroendocrine Neoplasias.

Project description:Gastroenteropancreatic neuroendocrine neoplasias are a diverse group of neoplasms with different characteristics in terms of site, biological behaviour and metastatic potential. In comparison to other cancers, they are genetically quiet, harbouring relatively few somatic mutations. It is increasingly becoming evident that epigenetic changes are as relevant, if not more so, as somatic mutations in promoting oncogenesis. Despite significant tumour heterogeneity, it is obvious that DNA methylation, histone and chromatin modifications and microRNA expression profiles are distinctive for GEP-NEN subtypes and may correlate with clinical outcome. This review summarises existing knowledge on epigenetic changes, identifying potential contributions to pathogenesis and oncogenesis. In particular, we focus on epigenetic changes pertaining to well-differentiated neuroendocrine tumours, which make up the bulk of NENs. We also highlight both similarities and differences within the subtypes of GEP-NETs and how these relate and compare to other types of cancers. We relate epigenetic understanding to existing treatments and explore how this knowledge may be exploited in the development of novel treatment approaches, such as in theranostics and combining conventional treatment modalities. We consider potential barriers to epigenetic research in GEP-NENs and discuss strategies to optimise research and development of new therapies.

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