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基于基因表达谱分析鉴定甲状腺乳头状癌的潜在生物标志物和药物。

Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis.

作者信息

Qu Ting, Li Yan-Ping, Li Xiao-Hong, Chen Yan

机构信息

Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Mol Med Rep. 2016 Dec;14(6):5041-5048. doi: 10.3892/mmr.2016.5855. Epub 2016 Oct 19.

Abstract

The present study aimed to systematically examine the molecular mechanisms of papillary thyroid cancer (PTC), and identify potential biomarkers and drugs for the treatment of PTC. Two microarray data sets (GSE3467 and GSE3678), containing 16 PTC samples and 16 paired normal samples, were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Analysis package. Subsequently, the common DEGs were screened for functional and pathway enrichment analysis using the Database for Annotation Visualization and Integrated Discovery. The representative interaction subnetwork was further derived using Molecular Complex Detection software. In addition, the potential drugs for the hub DEGs in the subnetwork were screened from DrugBank and the potential drug‑like ligands, which interacted with genes, were selected using MTiOpenScreen. A total of 167 common DEGs, including 77 upregulated and 90 downregulated DEGs, were screened. The common DEGs were associated with the functions of plasma membrane, extracellular matrix, response to steroid hormone stimulus and cell adhesion, and the pathways of tyrosine metabolism and cell adhesion molecules were significantly enriched. A total of eight common DEGs (MET, SERPINA1, LGALS3, FN1, TNFRSF11B, LAMB3 and COL13A1) were involved in the subnetwork. The two drugs, lanoteplase and ocriplasmin, and four drugs, β‑mercaptoethanol, recombinant α 1‑antitrypsin, PPL‑100 and API, were found for FN1 and SERPINA1, respectively. The common DEGs identified may be potential biomarkers for PCT. FN1 and SERPINA1 may be involved in PTC by regulating epithelial‑to‑mesenchymal transition and responding to steroid hormone stimuli, respectively. Ocriplasmin, β‑mercaptoethanol and recombinant α 1‑antitrypsin may be potential drugs for the treatment of PTC.

摘要

本研究旨在系统地探究甲状腺乳头状癌(PTC)的分子机制,并识别用于治疗PTC的潜在生物标志物和药物。从基因表达综合数据库下载了两个微阵列数据集(GSE3467和GSE3678),其中包含16个PTC样本和16对正常样本。使用微阵列分析的线性模型软件包识别差异表达基因(DEG)。随后,使用注释可视化与整合发现数据库对常见的DEG进行功能和通路富集分析。使用分子复合物检测软件进一步推导代表性的相互作用子网。此外,从药物银行筛选子网中枢纽DEG的潜在药物,并使用MTiOpenScreen选择与基因相互作用的潜在类药物配体。共筛选出167个常见的DEG,包括77个上调的DEG和90个下调的DEG。常见的DEG与质膜、细胞外基质、对类固醇激素刺激的反应和细胞黏附功能相关,酪氨酸代谢和细胞黏附分子通路显著富集。共有8个常见的DEG(MET、SERPINA1、LGALS3、FN1、TNFRSF11B、LAMB3和COL13A1)参与了子网。分别为FN1和SERPINA1找到了两种药物,即拉诺替普酶和奥曲普酶,以及四种药物,即β-巯基乙醇、重组α1-抗胰蛋白酶、PPL-100和API。所识别的常见DEG可能是PCT的潜在生物标志物。FN1和SERPINA1可能分别通过调节上皮-间质转化和对类固醇激素刺激作出反应而参与PTC。奥曲普酶、β-巯基乙醇和重组α1-抗胰蛋白酶可能是治疗PTC的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/5355717/e60a3a14b4cf/MMR-14-06-5041-g00.jpg

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