Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China.
Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China.
Dig Dis Sci. 2020 Oct;65(10):2884-2895. doi: 10.1007/s10620-019-06014-6. Epub 2020 Jan 1.
Circular RNAs (circRNAs) could play carcinogenic roles in gastric cancer (GC) and have potential to be biomarkers for GC early diagnosis, which needs to be further excavated and supported by more evidence.
The study aims to identify more authentic circRNA expression profiles that could function as potential biomarkers in GC.
circRNA expression data in three microarrays were downloaded from Gene Expression Omnibus datasets. A systematic meta-analysis based on an integrated dataset pre-processed from the three microarrays was conducted to identify a panel of differentially expressed circRNAs (DEcircs) by using the metaDE package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment were used to note the corresponding functions of DEcircs. Quantitative real-time polymerase chain reaction was applied to verify the DEcircs expression in cancer tissues and adjacent paracancerous tissues. A GC risk-related circRNAs-miRNAs-mRNAs network was further constructed and analyzed.
MetaDE analysis suggested 64 DEcircs between cancer tissues and adjacent normal tissues. GO and KEGG analysis showed that the parental genes of these DEcircs were mainly associated with histone methylation, Wnt signalosome and histone methylation activity. Hsa_circ_0005927 and hsa_circ_0067934 were verified in GC tissues, and a GC risk-related network was constructed.
MetaDE-based circRNA expression profiles revealed a series of potential biomarkers involved in GC. Two circRNAs, hsa_circ_0005927 and hsa_circ_0067934, could be more authentic biomarkers for GC screening. The GC risk-related network of hsa_circ_0005927/hsa_circ_0067934 and their downstream targets will provide new genetic insights for GC research.
环状 RNA（circRNAs）在胃癌（GC）中可能发挥致癌作用，并有可能成为 GC 早期诊断的生物标志物，这需要更多的证据来进一步挖掘和支持。
本研究旨在确定更多真实的 circRNA 表达谱，这些表达谱可作为 GC 的潜在生物标志物。
从基因表达综合数据库（GEO）数据集下载了三个微阵列的 circRNA 表达数据。通过使用 metaDE 包对三个微阵列预处理的综合数据集进行系统的荟萃分析，确定一组差异表达的 circRNAs（DEcircRNAs）。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）术语富集来注释 DEcircRNAs 的相应功能。采用实时定量聚合酶链反应（qRT-PCR）验证癌组织和癌旁组织中 DEcircRNAs 的表达情况。进一步构建和分析 GC 相关 circRNAs-miRNAs-mRNAs 网络。
metaDE 分析提示癌症组织与癌旁正常组织之间存在 64 个 DEcircRNAs。GO 和 KEGG 分析表明，这些 DEcircRNAs 的母基因主要与组蛋白甲基化、Wnt 信号通路和组蛋白甲基化活性有关。在 GC 组织中验证了 hsa_circ_0005927 和 hsa_circ_0067934，并构建了一个 GC 风险相关的网络。
基于 metaDE 的 circRNA 表达谱揭示了一系列与 GC 相关的潜在生物标志物。两个 circRNAs，hsa_circ_0005927 和 hsa_circ_0067934，可能是 GC 筛查更可靠的生物标志物。hsa_circ_0005927/hsa_circ_0067934 及其下游靶标与 GC 风险相关的网络将为 GC 研究提供新的遗传见解。
