ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2016
Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Multiomic analyses delineate human neuroendocrine tumor cell states in relation to normal enteroendocrine cell ontogeny.The Journal of clinical investigation · 2026Article
- Spatial Transcriptomics Reveals Location-Specific Tumor Cell Subtypes and Signaling within Multifocal Small Intestinal Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Surgical management of small intestinal neuroendocrine tumours.The British journal of surgery · 2026Article
- The metastatic spectrum in functional and non-functional NENs: mechanistic insights from multi-omics.Frontiers in endocrinology · 2026Review
- Article
- Mechanistic role of miR-375 in regulating PDPK1 to promote progression of small bowel neuroendocrine tumors: a silico analysis.Discover oncology · 2025Article
- Small intestinal neuroendocrine tumors lack early genomic drivers, acquire DNA repair defects and harbor hallmarks of low REST expression.Scientific reports · 2025Article
- Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?Endocrine pathology · 2024Review
- Multifaceted modeling of small intestinal neuroendocrine tumors.Endocrine oncology (Bristol, England) · 2024Review
- Identification of TIMP1-induced dysregulation of epithelial-mesenchymal transition as a key pathway in inflammatory bowel disease and small intestinal neuroendocrine tumors shared pathogenesis.Frontiers in genetics · 2024Article
- HSP90 expression is associated with outcome in pulmonary carcinoid tumor patients.Translational lung cancer research · 2023Article
- Spatial and temporal heterogeneity of digestive neuroendocrine neoplasms.Therapeutic advances in medical oncology · 2023Review
- Potential effective diagnostic biomarker in patients with primary and metastatic small intestinal neuroendocrine tumors.Frontiers in genetics · 2023Article
- Synthetic Antibodies Detect Distinct Cellular States of Chromosome Passenger Complex Proteins.Journal of molecular biology · 2022Article
- Pralsetinib: chemical and therapeutic development with FDA authorization for the management of RET fusion-positive non-small-cell lung cancers.Archives of pharmacal research · 2022Review
- Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics.Frontiers in molecular biosciences · 2022Review
- Genetic Drivers of Ileal Neuroendocrine Tumors.Cancers · 2021Review
- Assessment of hormonal levels as prognostic markers and of their optimal cut-offs in small intestinal neuroendocrine tumours grade 2.Endocrine · 2021Article
- Small Bowel Neuroendocrine Tumors.Current problems in surgery · 2020Article
- Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations.World journal of gastroenterology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We wanted to define the transcriptome of small intestinal neuroendocrine tumors in order to identify clinically relevant subgroups of tumors, prognostic markers and novel targets for treatment. Genome-wide expression profiling was conducted on tumor biopsies from 33 patients with well-differentiated neuroendocrine tumors of the distal ileum and metastatic disease at the time of diagnosis. Unsupervised hierarchical clustering analysis identified three groups of tumors. The largest group, comprising half of the tumors, was characterized by longer patient survival and higher expression of neuroendocrine markers, including SSTR2. Tumors with higher grade (G2/3) or gain of chromosome 14 were associated with shorter patient survival and increased expression of cell cycle-promoting genes. Pathway analysis predicted the prostaglandin E receptor 2 (PTGER2) as the most significantly activated regulator in tumors of higher grade, whereas Forkhead box M1 (FOXM1) was the most significantly activated regulator in tumors with gain of chromosome 14. Druggable genes identified from expression profiles included clinically proven SSTR2 and also novel targets, for example, receptor tyrosine kinases (RET, FGFR1/3, PDGFRB and FLT1), epigenetic regulators, molecular chaperones and signal transduction molecules. Evaluation of candidate drug targets on neuroendocrine tumors cells (GOT1) showed significant inhibition of tumor cell growth after treatment with tyrosine kinase inhibitors or inhibitors of HDAC, HSP90 and AKT. In conclusion, we have defined the transcriptome of small intestinal neuroendocrine tumors and identified novel subgroups with clinical relevance. We found specific gene expression patterns associated with tumor grade and chromosomal alterations. Our data also suggest novel prognostic biomarkers and therapies for these patients.
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