Screening key candidate genes and pathways involved in insulinoma by microarray analysis

Abstract

Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues.A total of 1632 DEGs were obtained, including 1117 upregulated genes and 514 downregulated genes. Pathway enrichment results showed that upregulated DEGs were significantly implicated in insulin secretion, and downregulated DEGs were mainly enriched in pancreatic secretion. PPI network analysis revealed 7 hub genes with degrees more than 10, including GCG (glucagon), GCGR (glucagon receptor), PLCB1 (phospholipase C, beta 1), CASR (calcium sensing receptor), F2R (coagulation factor II thrombin receptor), GRM1 (glutamate metabotropic receptor 1), and GRM5 (glutamate metabotropic receptor 5). DEGs involved in the significant modules were enriched in calcium signaling pathway, protein ubiquitination, and platelet degranulation. Quantitative RT-PCR data confirmed that the expression trends of these hub genes were similar to the results of bioinformatic analysis.The present study demonstrated that candidate DEGs and enriched pathways were the potential critical molecule events involved in the development of insulinoma, and these findings were useful for better understanding of insulinoma genesis.

<em>In&nbsp;silico</em> prediction and validation of potential therapeutic genes in pancreatic &beta;‑cells associated with type 2 diabetes

“…Microarray analysis of T2D, combining network pharmacology with bioinformatics methods, provides a promising strategy to identify molecular biological information, and are also powerful tools for the development of anti-T2D targets (19). A large amount of core data on complex diseases, such as T2D, has been produced from gene combining chromatin immunoprecipitation, which are uploaded on the Gene Expression Omnibus (GEO) public database of the National Center of Biotechnology Information (20). Furthermore, extracting and re-analyzing molecular data can provide a valuable perspective on understanding the molecular mechanisms of complex diseases (20).…”

“…A large amount of core data on complex diseases, such as T2D, has been produced from gene combining chromatin immunoprecipitation, which are uploaded on the Gene Expression Omnibus (GEO) public database of the National Center of Biotechnology Information (20). Furthermore, extracting and re-analyzing molecular data can provide a valuable perspective on understanding the molecular mechanisms of complex diseases (20).…”

Genetic predictors of insulin-producing pancreatic tumor

“…Однако у больного было зафиксировано снижение суточной экскреции кальция с мочой, соответственно, диагностирована семейная гипокальциурическая гиперкальциемия. При генетическом исследовании не обнаружено изменений в MEN1, но выявлена мутация в гене CASR (кодирует кальцийчувствительный рецептор, расположенный в плазматической мембране и регулирующий процессы воспаления, секреции гормонов, экспрессии генов, пролиферации, дифференцировки и апоптоза [18]), патогномоничная для семейной гипокальциурической гиперкальциемии. При этом в образцах ткани инсулиномы и метастазов обнаружена экспрессия мРНК CASR, а также белка, кодируемого данным геном.…”

“…Это предположение подтверждается данными W. Zhou и соавт. [18], которые обнаружили увеличение экспрессии данного гена по сравнению с нормальной панкреатической тканью. Более того, авторы подчеркивают: CASR является геном-концентратором, то есть регулирует экспрессию большого числа других генов.…”

“…При сравнении экспрессии генов в образцах ткани инсулиномы и нормальной панкреатической ткани было выявлено 1117 генов с повышением экспрессии и 514 генов -с уменьшением [18]. При этом анализ белок-белкового взаимодействия идентифицировал 7 генов-концентраторов: РНК 26 инсулином обнаружили мутации в следующих генах: KDM6A (кодирует лизин-специфическую деметилазу), FLNC (кодирует филамин С), ATR (кодирует серин/треониновую протеинкиназу ATR), ARHGAP35 (кодирует белки, активирующие гуанозин-5'-трифосфатазную активность RhoA).…”