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鉴定循环 miR-551b-5p 在胃癌中的诊断效用和分子机制。

Identification of diagnostic utility and molecular mechanisms of circulating miR-551b-5p in gastric cancer.

机构信息

Digestive Department, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.

Biomedical Sciences Department, University of Tennessee Health Sciences Center, Memphis, TN, 38105, USA.

出版信息

Pathol Res Pract. 2019 May;215(5):900-904. doi: 10.1016/j.prp.2019.01.035. Epub 2019 Jan 28.

Abstract

BACKGROUND

Gastric cancer (GC) is one of the most common cancers globally leading to 850,000 deaths each year. GC patients are often diagnosed at advanced stages which results in poor prognosis. This study aimed to identify a novel circulating miRNA as the diagnostic biomarker of GC and further explore its regulatory mechanisms in GC.

MATERIALS AND METHODS

First, the candidate serum miRNA was selected after analysis of microarray data. Then, the levels of candidate miRNA in the serum of GC patients were validated in an independent cohort. The diagnostic utility of miRNA was evaluated by using receiver operating characteristic curve (ROC) analysis. The functional and pathways enrichment analysis of targets of candidate miRNA were explored by online tool DAVID.

RESULTS

After comprehensive analysis of Gene Expression Omnibus (GEO) dataset, miR-551b-5p was selected as candidate due to its highest differential fold-change. Another independent cohort showed that serum miR-551b-5p could differentiate GC patients from healthy controls (HCs) with area under the curve (AUC) of 0.84 (95%CI: 0.75-0.93). The functional and pathways enrichment analysis revealed that targets of miR-551b-5p mainly located in cytoplasm and significantly associated with regulation of ubiquitin-dependent protein catabolic process, cell division, and mRNA stability.

CONCLUSIONS

Circulating miR-551b-5p was a novel promising biomarker for the detection of GC and exploration of the molecular mechanisms of miR-551b-5p is useful to search for new therapeutic strategies of GC.

摘要

背景

胃癌(GC)是全球最常见的癌症之一,每年导致 85 万人死亡。GC 患者通常在晚期被诊断,导致预后不良。本研究旨在确定一种新型循环 miRNA 作为 GC 的诊断生物标志物,并进一步探讨其在 GC 中的调控机制。

材料和方法

首先,通过微阵列数据分析选择候选血清 miRNA。然后,在独立队列中验证 GC 患者血清中候选 miRNA 的水平。通过使用接收器操作特征曲线(ROC)分析评估 miRNA 的诊断效用。通过在线工具 DAVID 探索候选 miRNA 靶标的功能和途径富集分析。

结果

经过综合基因表达综合数据库(GEO)数据集分析,选择 miR-551b-5p 作为候选物,因为其差异折叠变化最高。另一个独立队列表明,血清 miR-551b-5p 可以区分 GC 患者与健康对照(HC),曲线下面积(AUC)为 0.84(95%CI:0.75-0.93)。功能和途径富集分析表明,miR-551b-5p 的靶标主要位于细胞质中,与泛素依赖性蛋白降解过程、细胞分裂和 mRNA 稳定性的调节显著相关。

结论

循环 miR-551b-5p 是一种新型有前途的 GC 检测生物标志物,探索 miR-551b-5p 的分子机制有助于寻找 GC 的新治疗策略。

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