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枢纽基因对肺腺癌临床病理及预后特征的影响。

Effects of hub genes on the clinicopathological and prognostic features of lung adenocarcinoma.

作者信息

Yu Dong-Hu, Huang Jing-Yu, Liu Xiao-Ping, Ruan Xiao-Lan, Chen Chen, Hu Wei-Dong, Li Sheng

机构信息

Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

出版信息

Oncol Lett. 2020 Feb;19(2):1203-1214. doi: 10.3892/ol.2019.11193. Epub 2019 Dec 9.

Abstract

Lung adenocarcinoma (LUAD) is a common malignancy; however, the majority of its underlying molecular mechanisms remain unknown. In the present study, weighted gene co-expression network analysis was applied to construct gene co-expression networks for the GSE19804 dataset, in order to screen hub genes associated with the pathogenesis of LUAD. In addition, with the aid of the Database for Annotation, Visualization and Integrated Discovery, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes, pathway enrichment analyses were performed on the genes in the selected module. Using the GSE40791 dataset and The Cancer Genome Atlas database, the hub genes were identified. It was discovered that the turquoise module was the most significant module associated with the tumor stage of LUAD. After performing functional enrichment analyses, it was indicated that the turquoise module was mainly enriched in signal transduction. Additionally, at the transcriptional and translational level, nine hub genes were identified and validated: Carbonic anhydrase 4 (CA4), platelet and endothelial cell adhesion molecule 1 (PECAM1), DnaJ member B4 (DNAJB4), advanced glycosylation end-product specific receptor (AGER), GTPase, IMAP family member 6 (GIMAP6), chromosome 10 open reading frame 54 (C10orf54), dedicator of cytokinesis 4 (DOCK4), Golgi membrane protein 1 (GOLM1) and platelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3). CA4, PECAM1, DNAJB4, AGER, GIMAP6, C10orf54 and DOCK4 were expressed at lower levels in the tumor samples, whereas GOLM1 and PAFAH1B3 were highly expressed in tumor samples. In addition, all hub genes were associated with prognosis. In conclusion, one module and nine genes were recognized to be associated with the tumor stage of LUAD. These findings may enhance the understanding of the progression and prognosis of LUAD.

摘要

肺腺癌(LUAD)是一种常见的恶性肿瘤;然而,其大多数潜在分子机制仍不清楚。在本研究中,应用加权基因共表达网络分析为GSE19804数据集构建基因共表达网络,以筛选与LUAD发病机制相关的枢纽基因。此外,借助注释、可视化与整合发现数据库、基因本体论和京都基因与基因组百科全书,对所选模块中的基因进行通路富集分析。利用GSE40791数据集和癌症基因组图谱数据库,确定了枢纽基因。发现绿松石模块是与LUAD肿瘤分期最相关的模块。进行功能富集分析后表明,绿松石模块主要富集于信号转导。此外,在转录和翻译水平上,鉴定并验证了9个枢纽基因:碳酸酐酶4(CA4)、血小板和内皮细胞黏附分子1(PECAM1)、DnaJ成员B4(DNAJB4)、晚期糖基化终产物特异性受体(AGER)、GTP酶、IMAP家族成员6(GIMAP6)、10号染色体开放阅读框54(C10orf54)、胞质分裂 dedicator 4(DOCK4)、高尔基体膜蛋白1(GOLM1)和血小板活化因子乙酰水解酶1b催化亚基3(PAFAH1B3)。CA4、PECAM1、DNAJB4、AGER、GIMAP6、C10orf54和DOCK4在肿瘤样本中的表达水平较低,而GOLM1和PAFAH1B3在肿瘤样本中高表达。此外,所有枢纽基因均与预后相关。总之,确定了一个模块和九个基因与LUAD的肿瘤分期相关。这些发现可能会增进对LUAD进展和预后的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c191/6956410/5229487845db/ol-19-02-1203-g00.jpg

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