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胃癌患者血浆 miRNA 和长链非编码 RNA 的共表达谱分析。

Co-expression profiling of plasma miRNAs and long noncoding RNAs in gastric cancer patients.

机构信息

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

出版信息

Gene. 2019 Mar 1;687:135-142. doi: 10.1016/j.gene.2018.11.034. Epub 2018 Nov 14.

Abstract

PURPOSE

The recent researches indicate that differential non-coding RNAs expression signatures could be associated with the pathogenesis of gastric cancer (GC). However, there are few studies focused on lncRNA-miRNAs co-expression profiling in GC patients. Therefore, in the present study the expression of H19 and MEG3 and their related miRNAs including miR-148a-3p, miR-181a-5p, miR-675-5p and miR-141-3p were determined in the plasma samples of GC patients and controls.

MATERIALS AND METHODS

This case-control study included 62 GC patients and 40 age- sex matched controls. The non-coding RNA levels were assessed by real-time PCR. Further, using in silico analysis, we identified shared targets of studied miRNAs and performed GC-associated pathway enrichment analysis.

RESULTS

Our results showed that the H19 level was significantly (P = 0.008) elevated and MEG3 expression was significantly (P = 0.002) down-regulated in GC patients compared to healthy participants. Furthermore, it was revealed that the miR-675-5p level was increased, while miR-141-3p plasma levels were significantly reduced in GC patients (P < 0.05). We did not observe a significant difference for miR-148a-3p (P = 0.682) and miR-181a-5p (P = 0.098) expression between groups. In addition, the expression levels of H19, MEG3 and miR-148a-3p were associated with some clinicopathological features of patients (P < 0.05). ROC analysis revealed that a combination of H19, MEG3 and miR-675-5p levels able to discriminate controls and GC subjects with 88.87% sensitivity and 85% specificity (AUC, 0.927; 0.85-0.96 CI, P < 0.0001).

CONCLUSION

The results of current study demonstrated that combination of H19, MEG3 and miR-675-5p expression levels could provide a potential diagnostic panel for GC.

摘要

目的

最近的研究表明,差异非编码 RNA 表达谱可能与胃癌(GC)的发病机制有关。然而,目前很少有研究集中在 GC 患者的长链非编码 RNA-微小 RNA 共表达谱上。因此,在本研究中,我们检测了 GC 患者和对照者血浆样本中 H19 和 MEG3 及其相关 miRNA(miR-148a-3p、miR-181a-5p、miR-675-5p 和 miR-141-3p)的表达。

材料和方法

本病例对照研究纳入了 62 例 GC 患者和 40 名年龄、性别匹配的对照者。采用实时 PCR 检测非编码 RNA 水平。此外,通过计算机分析,我们鉴定了研究 miRNA 的共享靶标,并进行了与 GC 相关的途径富集分析。

结果

我们的结果表明,与健康参与者相比,GC 患者的 H19 水平显著升高(P=0.008),MEG3 表达显著降低(P=0.002)。此外,研究表明,GC 患者 miR-675-5p 水平升高,而 miR-141-3p 血浆水平显著降低(P<0.05)。我们未观察到 miR-148a-3p(P=0.682)和 miR-181a-5p(P=0.098)表达在两组间有显著差异。此外,H19、MEG3 和 miR-148a-3p 的表达水平与患者的一些临床病理特征相关(P<0.05)。ROC 分析显示,H19、MEG3 和 miR-675-5p 水平的组合能够以 88.87%的敏感性和 85%的特异性区分对照组和 GC 患者(AUC,0.927;0.85-0.96 CI,P<0.0001)。

结论

本研究结果表明,H19、MEG3 和 miR-675-5p 表达水平的组合可为 GC 提供一个潜在的诊断面板。

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