MetaDE-Based Analysis of circRNA Expression Profiles Involved in Gastric Cancer

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ORIGINAL ARTICLE

MetaDE‑Based Analysis of circRNA Expression Profiles Involved in Gastric Cancer Han‑xi Ding1,2 · Qian Xu1,2 · Ben‑gang Wang1,2,3 · Zhi Lv1,2 · Yuan Yuan1,2  Received: 21 August 2019 / Accepted: 12 December 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Background  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. Aims  The study aims to identify more authentic circRNA expression profiles that could function as potential biomarkers in GC. Methods  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. Results  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. Conclusion  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 riskrelated network of hsa_circ_0005927/hsa_circ_0067934 and their downstream targets will provide new genetic insights for GC research. Keywords  Circular RNA · Stomach neoplasm (gastric cancer) · Bioinformatics · MetaDE package · Microarray · Biomarkers Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1062​0-019-06014​-6) contains supplementary material, which is available to authorized users. * Yuan Yuan [email protected] Qian Xu [email protected] 1



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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 Hepatobiliary Surgery Department of General Surgery Institute, The First Hospital of China Medical University, Shenyang, China

Abbreviations GC Gastric cancer qRT-PCR Quantitative real-time polymerase chain reaction GEO Gene expression omnibus FC Fold change GO Gene ontology KEGG Kyoto Encyclopedia of Genes a