MicroRNA meta-signature of oral cancer: evidence from a meta-analysis

Katarina  Zeljic; Ivan  Jovanovic; Jasmina  Jovanovic; Zvonko  Magic; Aleksandra  Stankovic; Gordana  Supic

doi:10.1080/03009734.2018.1439551

Katarina Zeljic Faculty of Biology, University of Belgrade, Belgrade, Serbia http://orcid.org/0000-0002-6545-8616
Ivan Jovanovic Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Vinča Institute of Nuclear Sciences, Belgrade, Serbia http://orcid.org/0000-0001-7932-9463
Jasmina Jovanovic Faculty of Mathematics, University of Belgrade, Belgrade, Serbia
Zvonko Magic Faculty of Medicine, Military Medical Academy, University of Defence, Belgrade, Serbia; Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
Aleksandra Stankovic Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Vinča Institute of Nuclear Sciences, Belgrade, Serbia
Gordana Supic Faculty of Medicine, Military Medical Academy, University of Defence, Belgrade, Serbia; Institute for Medical Research, Military Medical Academy, Belgrade, Serbia

DOI: https://doi.org/10.1080/03009734.2018.1439551

Keywords: Enrichment analysis, meta-analysis, meta-signature, miRNA, oral cancer

Abstract

Aim: It was the aim of the study to identify commonly deregulated miRNAs in oral cancer patients by performing a meta-analysis of previously published miRNA expression profiles in cancer and matched normal non-cancerous tissue in such patients.

Material and methods: Meta-analysis included seven independent studies analyzed by a vote-counting method followed by bioinformatic enrichment analysis.

Results: Amongst seven independent studies included in the meta-analysis, 20 miRNAs were found to be deregulated in oral cancer when compared with non-cancerous tissue. Eleven miRNAs were consistently up-regulated in three or more studies (miR-21-5p, miR-31-5p, miR-135b-5p, miR-31-3p, miR-93-5p, miR-34b-5p, miR-424-5p, miR-18a-5p, miR-455-3p, miR-450a-5p, miR-21-3p), and nine were down-regulated (miR-139-5p, miR-30a-3p, miR-376c-3p, miR-885-5p, miR-375, miR-486-5p, miR-411-5p, miR-133a-3p, miR-30a-5p). The meta-signature of identified miRNAs was functionally characterized by KEGG enrichment analysis. Twenty-four KEGG pathways were significantly enriched, and TGF-beta signaling was the most enriched signaling pathway. The highest number of meta-signature miRNAs was involved in the sphingolipid signaling pathway. Natural killer cell-mediated cytotoxicity was the pathway with most genes regulated by identified miRNAs. The rest of the enriched pathways in our miRNA list describe different malignancies and signaling.

Conclusions: The identified miRNA meta-signature might be considered as a potential battery of biomarkers when distinguishing oral cancer tissue from normal, non-cancerous tissue. Further mechanistic studies are warranted in order to confirm and fully elucidate the role of deregulated miRNAs in oral cancer.

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