Dataset Information

Expression profiling of small intestinal neuroendocrine tumors identified pathways and gene networks linked to tumorigenesis and metastasis.

ABSTRACT: Small intestinal neuroendocrine tumors (SI-NETs) remain the most common subset in gastrointestinal neuroendocrine tumors and featured by aggressiveness. However, the molecular feature of SI-NETs remains largely unclear with key genes and pathways yet to be identified. The gene expression profile GSE65286 was retrieved for analysis. Artificial neural networks (ANNs) were constructed for the hub genes network models. A total of 613 differentially expressed genes (DEGs) were identified between normal (N) and primary tumor (T) groups, whereas 61 DEGs were identified between T and liver metastases (LM) groups. The top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the DEGs of N versus T were fat digestion and absorption pathway. For T versus LM the top KEGG pathways were complement and coagulation. In gene set enrichment analysis (GSEA), five gene sets, including Notch signaling, inflammatory response, coagulation, KRAS signaling, and allograft rejection were significantly enriched in the T group. The hub genes in the DEGs of T versus LM included albumin, fibrinogen gamma chain, alpha 2-HS glycoprotein, transferrin and GC, vitamin D binding protein. A distinct correlational alteration of hub genes was observed between T and LM groups. In ANN analysis, ALB and TF were the top predictors of metastasis. Moreover, the expression of ALB? showed the highest support to T whereas ALB>15.97 supports LM. TF?7.54 showed the highest negative correlation to the T. This bioinformatics analysis provided insights on potential key pathways and genes networks involved in SI-NETs and established an ANN-based hub gene model for metastatic prediction.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7298166 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression profiling of small intestinal neuroendocrine tumors identified pathways and gene networks linked to tumorigenesis and metastasis.

Wang Qiang Q Yu Chaoran C

Bioscience reports 20200601 6

Small intestinal neuroendocrine tumors (SI-NETs) remain the most common subset in gastrointestinal neuroendocrine tumors and featured by aggressiveness. However, the molecular feature of SI-NETs remains largely unclear with key genes and pathways yet to be identified. The gene expression profile GSE65286 was retrieved for analysis. Artificial neural networks (ANNs) were constructed for the hub genes network models. A total of 613 differentially expressed genes (DEGs) were identified between norm ...[more]

PMID: 32496505

Similar Datasets

Project description:BackgroundPatients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear.MethodsUtilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/- mouse model was used to detect entero-endocrine cell hyperplasia with IHC.ResultsAnalyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/- mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease.ConclusionsHemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs.

Dataset Information

Expression profiling of small intestinal neuroendocrine tumors identified pathways and gene networks linked to tumorigenesis and metastasis.

Publications

Expression profiling of small intestinal neuroendocrine tumors identified pathways and gene networks linked to tumorigenesis and metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets