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采用基因芯片预测分析方法鉴定具有诊断价值的垂体腺瘤潜在生物标志物

Identification of Potential Biomarkers with Diagnostic Value in Pituitary Adenomas Using Prediction Analysis for Microarrays Method.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

出版信息

J Mol Neurosci. 2019 Nov;69(3):399-410. doi: 10.1007/s12031-019-01369-x. Epub 2019 Jul 6.

Abstract

Pituitary adenomas are the most common intrasellar tumors. Patients should be identified at an early stage so that effective treatment can be implemented. The study aims at detecting the potential biomarkers with diagnostic value of pituitary adenomas. Using a total of seven gene expression profiles (GEPs) of the datasets from the Gene Expression Omnibus (GEO) database, we first screened 1980 significant differentially expressed genes (DEGs). Then, we employed the prediction analysis for microarray (PAM) algorithm to identify 340 significant DEGs able to differ pituitary tumor from normal samples, which include 208 upregulated DEGs and 132 downregulated DEGs. DAVID database was used to carry out the enrichment analysis on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways. We found that upregulated candidates were enriched in protein folding and metabolic pathways. Downregulated DEGs saw a significant enrichment in insulin receptor signaling pathway and hedgehog signaling pathway. Based on the protein-protein interaction (PPI) network as well as module analysis, we determined ten hub genes including PHLPP, ENO2, ACTR1A, EHHADH, EHMT2, FOXO1, DLD, CCT2, CSNK1D, and CETN2 that could be potential biomarkers with diagnostic value in pituitary adenomas. In conclusion, the study contributes to reliable and potential molecular biomarkers with diagnostic value. Moreover, these potential biomarkers may be used for prognosis and new therapeutic targets for the pituitary adenomas.

摘要

垂体腺瘤是最常见的鞍内肿瘤。患者应尽早发现,以便实施有效治疗。本研究旨在寻找具有诊断价值的垂体腺瘤潜在生物标志物。我们使用来自基因表达综合数据库(GEO)的七个基因表达谱(GEP)数据集,首先筛选出 1980 个显著差异表达基因(DEGs)。然后,我们采用微阵列预测分析(PAM)算法,鉴定出 340 个能区分垂体肿瘤与正常样本的显著 DEGs,其中包括 208 个上调 DEGs 和 132 个下调 DEGs。我们使用京都基因与基因组百科全书(KEGG)和基因本体论(GO)通路富集分析数据库对 DAVID 数据库进行了富集分析。我们发现上调候选基因富集在蛋白质折叠和代谢途径中。下调的 DEGs 在胰岛素受体信号通路和 hedgehog 信号通路中显著富集。基于蛋白质-蛋白质相互作用(PPI)网络和模块分析,我们确定了十个枢纽基因,包括 PHLPP、ENO2、ACTR1A、EHADH、EHMT2、FOXO1、DLD、CCT2、CSNK1D 和 CETN2,它们可能是具有诊断价值的垂体腺瘤潜在生物标志物。总之,本研究为具有诊断价值的可靠和潜在分子生物标志物做出了贡献。此外,这些潜在的生物标志物可能用于预测垂体腺瘤的预后和为其提供新的治疗靶点。

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