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