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基于生物信息学分析鉴定喉癌患者的核心 miRNA 预后标志物。

Identification of core miRNA prognostic markers in patients with laryngeal cancer using bioinformatics analysis.

机构信息

Department of Otorhinolaryngology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.

出版信息

Eur Arch Otorhinolaryngol. 2021 May;278(5):1613-1626. doi: 10.1007/s00405-020-06275-2. Epub 2020 Aug 12.

Abstract

PURPOSE

Lots of studies indicated that many microRNAs (miRNAs) are associated with the prognosis of patients with laryngeal cancer (LC). The objective of our study is to identify potential core miRNAs associated with the pathogenesis and prognosis of LC.

METHODS

Using the Cancer Genome Atlast database, we identified 70 differentially expressed miRNAs between LC tumor specimens and non-tumor specimens. Then Cox regression analyses and the least absolute shrinkage and selection operator regression signature were performed to detect miRNA prognostic markers. A nomogram integrating miRNA prognostic markers was constructed to predict overall survival (OS) for LC patients. The potential target genes of the key miRNA were predicted by miRTarBase and miRDB databases. Subsequently, their potential functions were revealed by gene ontology annotation and kyoto encyclopedia of genes and genomes pathway enrichment analysis. Related biological pathways of the key target gene involved in LC were detected through gene set enrichment analysis (GSEA).

RESULTS

A prognostic miRNA signature was constructed. The up-regulated miR-105-1 was related to a worse OS (p = 0.043), which suggested that miR-105-1 may likely be the key miRNA prognostic marker. Survival analyses and paired expression analyses of target genes indicated that ENDOU may be the key target gene. Finally, we conducted GSEA to elucidate the pathways enriched between low- and high-ENDOU expression datasets.

CONCLUSION

Our findings might bring some new light on the pathogenesis of LC. Then, it might facilitate doctors to predict the prognosis and improve treatment outcomes for LC patients. However, the behaviors of LC are relatively heterogeneous, and the TCGA database cannot provide detailed information about the subsites and treatment modalities of LC. Further molecular biological experiments and clinical investigations would be required to confirm this conclusion.

摘要

目的

大量研究表明,许多 microRNAs(miRNAs)与喉癌(LC)患者的预后相关。本研究旨在鉴定与 LC 发病机制和预后相关的潜在核心 miRNAs。

方法

我们使用癌症基因组图谱数据库,鉴定了 LC 肿瘤标本与非肿瘤标本之间的 70 个差异表达 miRNAs。然后进行 Cox 回归分析和最小绝对收缩和选择算子回归特征以检测 miRNA 预后标志物。构建整合 miRNA 预后标志物的列线图,以预测 LC 患者的总生存期(OS)。通过 miRTarBase 和 miRDB 数据库预测关键 miRNA 的潜在靶基因。随后,通过基因本体注释和京都基因与基因组百科全书通路富集分析揭示其潜在功能。通过基因集富集分析(GSEA)检测关键靶基因在 LC 中涉及的相关生物学通路。

结果

构建了一个预后 miRNA 特征。上调的 miR-105-1 与更差的 OS 相关(p=0.043),表明 miR-105-1 可能是关键的 miRNA 预后标志物。靶基因的生存分析和配对表达分析表明,ENDOU 可能是关键靶基因。最后,我们进行了 GSEA 以阐明低和高 ENDOU 表达数据集之间富集的通路。

结论

我们的研究结果可能为 LC 的发病机制提供新的思路。然后,它可能有助于医生预测 LC 患者的预后,并改善治疗结果。然而,LC 的行为相对异质性,TCGA 数据库不能提供 LC 亚部位和治疗方式的详细信息。需要进一步的分子生物学实验和临床研究来证实这一结论。

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