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Updated: Aug 1, 2025

Establishment and Characterization of Small Bowel Neuroendocrine Tumor Spheroids
Published on: October 14, 2019
Potential effective diagnostic biomarker in patients with primary and metastatic small intestinal neuroendocrine
Jianxian Chen1, Yiliang Meng1, Xiaojuan Huang1
1Department of Oncology, The People's Hospital of Baise, Baise, Guangxi, China.
Abstract:
Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignant tumors of the small intestine, with many patients presenting with metastases and their incidence increasing. We aimed to find effective diagnostic biomarkers for patients with primary and metastatic SI-NETs that could be applied for clinical diagnosis. Methods: We downloaded GSE65286 (training set) and GSE98894 (test set) from the GEO database and performed differential gene expression analysis to obtain differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs). The functions and pathways involved in these genes were further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, a global regulatory network involving dysregulated genes in SI-NETs was constructed based on RNAInter and TRRUST v2 databases, and the diagnostic power of hub genes was identified by receiver operating characteristic curve (ROC). Results: A total of 2,969 DEGs and DElncRNAs were obtained in the training set. Enrichment analysis revealed that biological processes (BPs) and KEGG pathways were mainly associated with cancer. Based on gene set enrichment analysis (GSEA), we obtained five BPs (cytokinesis, iron ion homeostasis, mucopolysaccharide metabolic process, platelet degranulation and triglyceride metabolic process) and one KEGG pathway (ppar signaling pathway). In addition, the core set of dysregulated genes obtained included MYL9, ITGV8, FGF2, FZD7, and FLNC. The hub genes were upregulated in patients with primary SI-NETs compared to patients with metastatic SI-NETs, which is consistent with the training set. Significantly, the results of ROC analysis showed that the diagnostic power of the hub genes was strong in both the training and test sets. Conclusion: In summary, we constructed a global regulatory network in SI-NETs. In addition, we obtained the hub genes including MYL9, ITGV8, FGF2, FZD7, and FLNC, which may be useful for the diagnosis of patients with primary and metastatic SI-NETs.
Insights
This study identified key genes (MYL9, ITGV8, FGF2, FZD7, FLNC) that can help diagnose primary and metastatic small intestinal neuroendocrine tumors (SI-NETs). These identified hub genes show strong diagnostic potential for clinical applications.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignant small intestine tumors, with increasing incidence and frequent metastasis.
- Effective diagnostic biomarkers are needed for both primary and metastatic SI-NETs to improve clinical management.
Purpose of the Study:
- To identify novel diagnostic biomarkers for primary and metastatic small intestinal neuroendocrine tumors (SI-NETs).
- To construct a global regulatory network for SI-NETs to understand underlying molecular mechanisms.
Main Methods:
- Differential gene and long non-coding RNA expression analysis using GEO datasets (GSE65286, GSE98894).
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore gene functions and pathways.
- Construction of a regulatory network and identification of hub genes using RNAInter and TRRUST v2 databases, validated by Receiver Operating Characteristic (ROC) curve analysis.
Main Results:
- Identified 2,969 differentially expressed genes and long non-coding RNAs in SI-NETs.
- Enrichment analyses indicated associations with cancer-related biological processes and the ppar signaling pathway.
- Five hub genes (MYL9, ITGV8, FGF2, FZD7, FLNC) were identified, showing upregulation in primary SI-NETs compared to metastatic ones and demonstrating strong diagnostic power in both training and test datasets.
Conclusions:
- A global regulatory network for SI-NETs was successfully constructed.
- The identified hub genes (MYL9, ITGV8, FGF2, FZD7, FLNC) hold significant potential as diagnostic biomarkers for primary and metastatic SI-NETs.

