Dataset Information

Visual analytics identifies key miRNAs for differentiating peripancreatic paraganglioma and pancreatic neuroendocrine tumors.

ABSTRACT:

Introduction

Paragangliomas (PGL), a type of neuroendocrine tumor, pose a significant diagnostic challenge due to their potential for unpredictable locations and asymptomatic presentation. Misdiagnosis of peripancreatic PGLs, particularly as pancreatic neuroendocrine tumors (PANNETs), is a pressing issue as it can negatively impact both pre- and post-treatment decision-making. The aim of our study was to identify microRNA markers for the reliable differential diagnosis of peripancreatic PGLs and PANNETs, addressing a crucial unmet need in the field and advancing the standard of care for these patients.

Methods

Morphing projections tool was used to analyze miRNA data from PGL and PANNET tumors present in the TCGA database. The findings were validated using two additional databases: GSE29742 and GSE73367.

Results

Our research uncovered substantial differences in the miRNA expression profiles of PGL and PANNET, leading to the identification of 6 key miRNAs (miR-10b-3p, miR-10b-5p, and the miRNA families miR-200c/141 and miR-194/192) that can effectively differentiate between the two types of tumors.

Discussion

These miRNA levels hold potential as biomarkers for improved diagnosis, offering a solution to the diagnostic challenge posed by these tumors and potentially improving the standard of care for patients.

SUBMITTER: Enguita JM

PROVIDER: S-EPMC10299733 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Visual analytics identifies key miRNAs for differentiating peripancreatic paraganglioma and pancreatic neuroendocrine tumors.

Enguita Jose María JM Díaz Ignacio I García Diego D Cubiella Tamara T Chiara María-Dolores MD Valdés Nuria N

Frontiers in endocrinology 20230613

<h4>Introduction</h4>Paragangliomas (PGL), a type of neuroendocrine tumor, pose a significant diagnostic challenge due to their potential for unpredictable locations and asymptomatic presentation. Misdiagnosis of peripancreatic PGLs, particularly as pancreatic neuroendocrine tumors (PANNETs), is a pressing issue as it can negatively impact both pre- and post-treatment decision-making. The aim of our study was to identify microRNA markers for the reliable differential diagnosis of peripancreatic ...[more]

PMID: 37383401

Similar Datasets

Project description:BackgroundCurrent diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, are relatively stable, and can be measured in patient blood specimens. We performed a multi-stage study to identify and validate characteristic circulating miRNAs in patients with metastatic small intestine neuroendocrine tumors, and to assess associations between miRNA levels and survival.MethodsUsing a 742-miRNA panel, we identified candidate miRNAs similarly expressed in 19 small intestine neuroendocrine tumors and matched plasma samples. We refined our panel in an independent cohort of plasma samples from 40 patients with metastatic small intestine NET and 40 controls, and then validated this panel in a second, large cohort of 120 patients with metastatic small intestine NET and 120 independent controls.ResultsmiRNA profiling of 19 matched small intestine neuroendocrine tumors and matched plasma samples revealed 31 candidate miRNAs similarly expressed in both tissue and plasma. We evaluated expression of these 31 candidate miRNAs in 40 independent cases and 40 normal controls, and identified 4 miRNAs (miR-21-5p, miR-22-3p, miR-29b-3p, and miR-150-5p) that were differently expressed in cases and controls (p<0.05). We validated these 4 miRNAs in a separate, larger panel of 120 cases and 120 controls. We confirmed that high circulating levels of miR-22-3p (p<0.0001), high levels of miR 21-5p, and low levels of miR-150-5p (p=0.027) were associated with the presence of metastatic small intestine NET. While levels of 29b-3p were lower in cases than in controls in both the initial cohort and the validation cohort, the difference in the validation cohort did not reach statistical significance. We further found that high levels of circulating miR-21-5p, high levels of circulating miR-22-3p and low levels of circulating miR-150-5p were each independently associated with shorter overall survival. A combined analysis using all three markers was highly prognostic for survival (HR 0.47, 95% CI 0.27-0.82).ConclusionsOur study suggests that elevated circulating levels of miR-21-5p and miR-22-3p and low levels of miR-150-5p are characteristic in patients with metastatic small intestine neuroendocrine tumors, and further suggests that levels of these miRNAs are associated with overall survival. These observations provide the basis for further validation studies, as well as studies to assess the biological function of these miRNAs in small intestine neuroendocrine tumors.

Project description:BackgroundTumor transcriptomes contain information of critical value to understanding the different capacities of a cell at both a physiological and pathological level. In terms of clinical relevance, they provide information regarding the cellular "toolbox" e.g., pathways associated with malignancy and metastasis or drug dependency. Exploration of this resource can therefore be leveraged as a translational tool to better manage and assess neoplastic behavior. The availability of public genome-wide expression datasets, provide an opportunity to reassess neuroendocrine tumors at a more fundamental level. We hypothesized that stringent analysis of expression profiles as well as regulatory networks of the neoplastic cell would provide novel information that facilitates further delineation of the genomic basis of small intestinal neuroendocrine tumors.ResultsWe re-analyzed two publically available small intestinal tumor transcriptomes using stringent quality control parameters and network-based approaches and validated expression of core secretory regulatory elements e.g., CPE, PCSK1, secretogranins, including genes involved in depolarization e.g., SCN3A, as well as transcription factors associated with neurodevelopment (NKX2-2, NeuroD1, INSM1) and glucose homeostasis (APLP1). The candidate metastasis-associated transcription factor, ST18, was highly expressed (>14-fold, p < 0.004). Genes previously associated with neoplasia, CEBPA and SDHD, were decreased in expression (-1.5 - -2, p < 0.02). Genomic interrogation indicated that intestinal tumors may consist of two different subtypes, serotonin-producing neoplasms and serotonin/substance P/tachykinin lesions. QPCR validation in an independent dataset (n = 13 neuroendocrine tumors), confirmed up-regulated expression of 87% of genes (13/15).ConclusionsAn integrated cellular transcriptomic analysis of small intestinal neuroendocrine tumors identified that they are regulated at a developmental level, have key activation of hypoxic pathways (a known regulator of malignant stem cell phenotypes) as well as activation of genes involved in apoptosis and proliferation. Further refinement of these analyses by RNAseq studies of large-scale databases will enable definition of individual master regulators and facilitate the development of novel tissue and blood-based tools to better understand diagnose and treat tumors.

Dataset Information

Visual analytics identifies key miRNAs for differentiating peripancreatic paraganglioma and pancreatic neuroendocrine tumors.

Introduction

Methods

Results

Discussion

Publications

Visual analytics identifies key miRNAs for differentiating peripancreatic paraganglioma and pancreatic neuroendocrine tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets