MicroRNA profiling in different grading of gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
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PROVIDER: PRJNA557200 | ENA |
REPOSITORIES: ENA
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Project description:Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors presenting a wide spectrum of different clinical and biological characteristics. In these tumors, the histological evaluation is a crucial element of clinical management. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, is the most reliable predictor of prognosis. This scoring method is time-consuming and a high reproducibility cannot be achieved. Novel approaches are needed to support histological evaluation and prognosis. In this study, starting from a microarray analysis, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. Moreover, we identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, we found miR-96-5p that raised its expression levels from grade 1 to grade 3; inversely, its target FOXO1 was decrease from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET correlates their expression with grading showing a potential advantage of miRNA quantification to aid clinicians in the classification of common GEP-NETs subtypes.
2020-08-04 | GSE135034 | GEO
Project description: Not available
| S-EPMC5870128 | biostudies-literature
Project description:BackgroundNeuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of ~ 6.9/100,000. NETs arise throughout the body from cells of the diffuse endocrine system. More than half originate from endocrine cells of the gastrointestinal tract and the pancreas, thus being referred to as gastroenteropancreatic NETs (GEP NETs). The only treatment that offers a cure is surgery, however most patients are diagnosed with metastatic disease, and curative surgery is usually not an option.Since the majority of patients are not candidate for curative surgery, they can be offered long-term systemic treatment, for both symptomatic relief and tumor growth suppression. Evidence based treatment options include somatostatin analogues, everolimus (an mTOR inhibitor), sunitinib (a tyrosine kinase inhibitor), peptide receptor radionuclide therapy (PRRT), chemotherapy, etc., alone or combined with cytoreductive procedures (surgery or liver directed procedures). However, there is an increasing need for novel therapies. Other treatment options being investigated are immunotherapy and epigenetic assessment that may lead to more personalized interventions. Following first line therapy with somatostatin analogues, there is no clear information to date indicating a preferred treatment sequence, and therefore the treatment approach should be individualized based on each NET patient characteristics.ConclusionsNET patients are increasingly diagnosed throughout the world, usually with metastatic disease and requiring systemic therapy. We believe that each patient should be therefore thoroughly evaluated and individually discussed by a multidisciplinary and dedicated NET-expert team, updated with all treatment options including ongoing clinical trials, and before selecting the proper treatment sequence.
| S-EPMC6042326 | biostudies-literature
Project description:This phase IV trial evaluates how well giving standard of care (SOC) peptide receptor radionuclide therapy (PRRT) after SOC surgical removal of as much tumor as possible (debulking surgery) works in treating patients with grade 1 or 2, somatostatin receptor (SSTR) positive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have spread from where they first started (primary site) to the liver (hepatic metastasis). Lutetium Lu 177 dotatate is a radioactive drug that uses targeted radiation to kill tumor cells. Lutetium Lu 177 dotatate includes a radioactive form (an isotope) of the element called lutetium. This radioactive isotope (Lu-177) is attached to a molecule called dotatate. On the surface of GEP-NET tumor cells, a receptor called a somatostatin receptor binds to dotatate. When this binding occurs, the lutetium Lu 177 dotatate drug then enters somatostatin receptor-positive tumor cells, and radiation emitted by Lu-177 helps kill the cells. Giving lutetium Lu 177 dotatate after surgical debulking may better treat patients with grade 1/2 GEP-NETs
| 90389 | ecrin-mdr-crc
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: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:It is well known that the prevalence of malnutrition or risk of malnutrition in cancer patients is high, as well as its impact on different parameters such as hospitalization, survival or response to certain treatments. In patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NET), due to their heterogeneity and longer survival, it is expected that the prevalence of malnutrition is probably underdiagnosed, as well as the existence of a negative impact on different parameters (quality of life, survival). So far, the studies carried out on nutrition and NET are very scarce and none has been carried out so far in Spain.
Before being able to carry out nutritional intervention studies on these patients, it is necessary to know the reality of the nutritional status of patients with NETs in Spain. The main motivation for the NUTRIGETNE study is to evaluate the epidemiological status of nutrition in NETs in the spanish population. In addition to know the epidemiological picture, it is intended to study the nutritional status from different points of view: analytical, clinical, anthropometric, etc. Besides, the study of nutritional status will allow us to closely monitor the patients who have a higher risk of malnutrition and to propose early interventions for those, as well as the impact of their nutritional status on different parameters: survival, hospitalization, quality of life or responses to the treatments.
NUTRIGETNE is a cross-sectional, open and multicenter study in which the nutritional status of patients with GEP NET in Spain will be evaluated.
| 2385163 | ecrin-mdr-crc
Project description:Small intestinal neuroendocrine tumors (SI-NETs) arise from serotonin-producing enterochromaffin cells. SI-NETs are often well-differentiated tumors and most patients have regional or distant metastases at initial presentation. MicroRNAs (miRs) are post-transcriptional regulators which are important in diverse biological processes and can function as tumor suppressor genes or oncogenes. This study aims to identify an exclusive SI-NETs miR profile that may have a critical role in development, diagnosis, prognosis and progression of these malignancies.
2012-11-08 | E-MTAB-862 | biostudies-arrayexpress
Project description:Somatostatin receptors are overexpressed in GEP-NETs and can be visualized in vivo by radiolabeled somatostatin-analogs.
During the last decades, conventional scintigraphy using 111In-DTPA-Octreotide (often named somatostatin receptor scintigraphy or SRS) was considered as the gold standard nuclear imaging technique in the evaluation of GEP-NETs. However, SRS may be suboptimal in this clinical setting because of the low intrinsic resolution of the technique and its selectivity for SST2 only. Its overall sensitivity is estimated to 60-70% (per lesion analysis), even when using the most recent SPECT-CT cameras. MRI have also a higher sensitivity than CT and SRS for the detection of liver metastases from GEP-NETs.
In recent years, positron emission tomography (PET) imaging, a high resolution and sensitive technology, has gained an increasing role in oncology. It has also been evaluated in GEP-NETs with somatostatin agonists (SSTa) radiolabelled with Gallium-68 [68Ga], a positron emitter with very promising results. Its diagnostic sensitivity is clearly superior to SRS and many European centers have already replaced SRS by [68Ga]-PET-SSTa.
Currently, three different [68Ga]-coupled peptides can be used in trials: DOTA-TOC, DOTA-TATE and DOTA-NOC with excellent affinities for SST2 (IC50: 2.5; 0.2 and 1.9 nM, respectively). Sensitivities of DOTA-TOC and DOTA-TATE PET/CT are quite similar.
[68Ga]-DOTANOC which also binds to SST5 was recently found to detect significantly more lesions than the SST2-specific radiotracer [68Ga]-DOTATATE in patients with GEP-NETs but this requires further evaluation.
It is therefore important to determine the interest of [68Ga]-DOTANOC combined with the standard diagnosis strategy in GEP-NETs and evaluate medicoeconomic impact of adding [68Ga]-DOTANOC in the work-up of patients.
The investigators hypothesis is that [68Ga]-DOTANOC will modify the management in at least 20% of patients in a more adapted way according to the 2012 ENETS guidelines in comparison to the decision based on the standard imaging work up (multiphasic WB CT, liver MRI and SRS).
110 patients will be included prospectively in 5 different French experienced centers (Marseille, Bordeaux, Toulouse, Paris, Clermond-Ferrand).
| 2202581 | ecrin-mdr-crc