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mRNA 表达谱和 miRNA 表达谱的联合鉴定了喉鳞状细胞癌不同肿瘤分期的检测生物标志物。

A combination of mRNA expression profile and miRNA expression profile identifies detection biomarkers in different tumor stages of laryngeal squamous cell carcinoma.

机构信息

Department of Otolaryngology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7296-7304. doi: 10.26355/eurrev_201811_16266.

Abstract

OBJECTIVE

This study was conducted to investigate microRNA (miRNA) target regulations during the disease progression in laryngeal squamous cell carcinoma (LSCC) and identify biomarkers in different tumor stages.

MATERIALS AND METHODS

The mRNA dataset GSE59102 and miRNA dataset GSE70289 were used in this study. After pretreatment, differentially expressed genes/miRNAs (DEGs/DEMs) in different tumor stages (beginning vs. margin, advanced vs. margin, and beginning vs. advanced) were selected on the basis of their limma package. Then, the enrichment analysis for these DEGs was conducted using ClueGO. Protein-protein interaction (PPI) network analysis was performed on the basis of the BioGRID database. After prediction of target genes of DEMs according to three validated miRNA databases, an integrated miRNA target network and its pathways were drawn using the multiMiR package.

RESULTS

Numerous DEGs were identified in different tumor stages of LSCC (beginning vs. margin, advanced vs. margin, and beginning vs. advanced), and a set of 18 DEMs was identified. Cell cycle was the most significantly enriched pathway of the DEGs. Four hub nodes (MCM2, EGFR, CDK2, and CDK1) were highlighted in the PPI network. In the integrated miRNA target network, 2 miRNAs were predominant: hsa-miR-331-3p (2 predicted targets, E2F1 and TNFRSF10B) and has-miR-375 (1 predicted target, TNNI3). These genes were tied up with cell cycle or apoptosis pathway.

CONCLUSIONS

Several genes and miRNAs might be used as markers for LSCC in different tumor stages (e.g., MCM2, EGFR, CDK1, CDK2, hsa-miR-331-3p, hsa-miR-375). They might function through the involvement of the cell cycle pathway.

摘要

目的

本研究旨在探讨喉鳞状细胞癌(LSCC)疾病进展过程中 microRNA(miRNA)靶标调控,并鉴定不同肿瘤分期的生物标志物。

材料与方法

本研究使用了 mRNA 数据集 GSE59102 和 miRNA 数据集 GSE70289。经过预处理,根据 limma 包选择不同肿瘤阶段(起始与边缘、进展与边缘、起始与进展)之间的差异表达基因/miRNA(DEGs/DEMs)。然后,使用 ClueGO 对这些 DEGs 进行富集分析。根据 BioGRID 数据库进行蛋白质-蛋白质相互作用(PPI)网络分析。根据三个验证 miRNA 数据库预测 DEMs 的靶基因后,使用 multiMiR 包绘制整合 miRNA 靶标网络及其通路。

结果

在 LSCC 的不同肿瘤阶段(起始与边缘、进展与边缘、起始与进展)中鉴定到大量的 DEGs,并鉴定到一组 18 个 DEMs。细胞周期是 DEGs 最显著富集的通路。在 PPI 网络中突出显示了 4 个枢纽节点(MCM2、EGFR、CDK2 和 CDK1)。在整合 miRNA 靶标网络中,有 2 个 miRNA 占主导地位:hsa-miR-331-3p(2 个预测靶标,E2F1 和 TNFRSF10B)和 has-miR-375(1 个预测靶标,TNNI3)。这些基因与细胞周期或细胞凋亡通路有关。

结论

一些基因和 miRNA 可能可作为不同肿瘤阶段 LSCC 的标志物(例如,MCM2、EGFR、CDK1、CDK2、hsa-miR-331-3p、hsa-miR-375)。它们可能通过参与细胞周期通路发挥作用。

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