Ghatnatti Vikrant, Vastrad Basavaraj, Patil Swetha, Vastrad Chanabasayya, Kotturshetti Iranna
Department of Endocrinology, J N Medical College, Belagavi and KLE Academy of Higher Education & Research 590010, Karnataka, India.
Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India.
AIMS Neurosci. 2021 Feb 7;8(2):254-283. doi: 10.3934/Neuroscience.2021014. eCollection 2021.
Pituitary prolactinoma is one of the most complicated and fatally pathogenic pituitary adenomas. Therefore, there is an urgent need to improve our understanding of the underlying molecular mechanism that drives the initiation, progression, and metastasis of pituitary prolactinoma. The aim of the present study was to identify the key genes and signaling pathways associated with pituitary prolactinoma using bioinformatics analysis. Transcriptome microarray dataset GSE119063 was downloaded from Gene Expression Omnibus (GEO) database. Limma package in R software was used to screen DEGs. Pathway and Gene ontology (GO) enrichment analysis were conducted to identify the biological role of DEGs. A protein-protein interaction (PPI) network was constructed and analyzed by using HIPPIE database and Cytoscape software. Module analyses was performed. In addition, a target gene-miRNA regulatory network and target gene-TF regulatory network were constructed by using NetworkAnalyst and Cytoscape software. Finally, validation of hub genes by receiver operating characteristic (ROC) curve analysis. A total of 989 DEGs were identified, including 461 up regulated genes and 528 down regulated genes. Pathway enrichment analysis showed that the DEGs were significantly enriched in the retinoate biosynthesis II, signaling pathways regulating pluripotency of stem cells, ALK2 signaling events, vitamin D3 biosynthesis, cell cycle and aurora B signaling. Gene Ontology (GO) enrichment analysis showed that the DEGs were significantly enriched in the sensory organ morphogenesis, extracellular matrix, hormone activity, nuclear division, condensed chromosome and microtubule binding. In the PPI network and modules, SOX2, PRSS45, CLTC, PLK1, B4GALT6, RUNX1 and GTSE1 were considered as hub genes. In the target gene-miRNA regulatory network and target gene-TF regulatory network, LINC00598, SOX4, IRX1 and UNC13A were considered as hub genes. Using integrated bioinformatics analysis, we identified candidate genes in pituitary prolactinoma, which might improve our understanding of the molecular mechanisms of pituitary prolactinoma.
垂体泌乳素瘤是最复杂且具有致命致病性的垂体腺瘤之一。因此,迫切需要加深我们对驱动垂体泌乳素瘤发生、发展和转移的潜在分子机制的理解。本研究的目的是通过生物信息学分析确定与垂体泌乳素瘤相关的关键基因和信号通路。从基因表达综合数据库(GEO)下载转录组微阵列数据集GSE119063。使用R软件中的Limma包筛选差异表达基因(DEGs)。进行通路和基因本体(GO)富集分析以确定DEGs的生物学作用。使用HIPPIE数据库和Cytoscape软件构建并分析蛋白质-蛋白质相互作用(PPI)网络。进行模块分析。此外,使用NetworkAnalyst和Cytoscape软件构建靶基因- microRNA调控网络和靶基因-转录因子调控网络。最后,通过受试者工作特征(ROC)曲线分析验证枢纽基因。共鉴定出989个DEGs,包括461个上调基因和528个下调基因。通路富集分析表明,DEGs在视黄酸生物合成II、调节干细胞多能性的信号通路、ALK2信号事件、维生素D3生物合成、细胞周期和极光B信号通路中显著富集。基因本体(GO)富集分析表明,DEGs在感觉器官形态发生、细胞外基质、激素活性、核分裂、浓缩染色体和微管结合方面显著富集。在PPI网络和模块中,SOX2、PRSS45、CLTC、PLK1、B4GALT6、RUNX1和GTSE1被视为枢纽基因。在靶基因- microRNA调控网络和靶基因-转录因子调控网络中,LINC00598、SOX4、IRX1和UNC13A被视为枢纽基因。通过综合生物信息学分析,我们在垂体泌乳素瘤中鉴定出候选基因,这可能会增进我们对垂体泌乳素瘤分子机制的理解。