Dogan Berkcan, Gumusoglu Ece, Ulgen Ege, Sezerman Osman Ugur, Gunel Tuba
Department of Medical Genetics, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey.
Department of Translational Medicine, Institute of Health Sciences, Bursa Uludag University, Bursa 16059, Turkey.
Genomics Inform. 2022 Jun;20(2):e20. doi: 10.5808/gi.21067. Epub 2022 Jun 30.
Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsalet7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.
最近的研究集中于通过液体活检利用肿瘤材料对卵巢癌（OC）进行早期检测。微小RNA（miRNA）影响OC和信号通路的机制仍不清楚。本研究旨在通过使用pathfindR对先前验证的循环miRNA的靶基因进行可靠的功能分析。此外，还利用癌症基因组图谱和GTEx数据集中常见的miRNA靶基因进行了总生存分析和病理分期分析。我们之前的研究利用高通量技术验证了三种在OC患者血清中具有诊断价值的下调miRNA（hsa-miR-885-5p、hsa-miR-1909-5p和hsa-let7d-3p）。这些miRNA的预测靶基因从miRDB数据库（v6.0）中检索。pathfindR使用靶基因进行了面向活性子网的京都基因与基因组百科全书（KEGG）通路富集分析。pathfindR分析评估的KEGG通路富集表明，有24条通路与靶基因相关。泛素介导的蛋白水解、剪接体和Notch信号通路是p值最低的前三条通路（p<0.001）。在数据集中发现93个常见基因存在差异表达（p<0.05）。在总生存分析中未发现显著基因，但在病理分期分析中发现24个基因具有显著性（p<0.05）。我们的研究结果提供了计算机模拟证据，表明经验证有效的循环miRNA靶基因和富集的通路与OC相关，并在治疗诊断应用中具有潜在作用。需要进一步的实验研究来验证我们的结果，这最终将为OC管理中的转化应用提供新的视角。
