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

<b>Aim:</b> 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. <b>Material and methods:</b> Meta-analysis included seven independent studies analyzed by a vote-counting method followed by bioinformatic enrichment analysis. <b>Results:</b> 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. <b>Conclusions:</b> 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.

<b>研究目的：</b>本研究旨在通过对已发表的口腔癌患者癌组织与配对正常非癌组织的微RNA (miRNA) 表达谱进行荟萃分析，筛选出口腔癌患者中普遍存在表达失调的miRNA。<b>材料与方法：</b>本荟萃分析纳入7项独立研究，先采用计数投票法进行数据分析，随后开展生物信息学富集分析。<b>结果：</b>在纳入本荟萃分析的7项独立研究中，共鉴定出20种在口腔癌组织与非癌组织对比中存在表达失调的miRNA。其中11种miRNA在3项及以上研究中均呈持续上调状态，包括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；另有9种miRNA呈持续下调状态，包括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。本研究通过京都基因与基因组百科全书 (KEGG) 富集分析，对上述鉴定得到的miRNA荟萃特征进行功能注释。共富集得到24条显著富集的KEGG通路，其中转化生长因子β (TGF-β) 信号通路为富集程度最高的信号通路；参与鞘脂信号通路的miRNA荟萃特征数量最多。自然杀伤细胞介导的细胞毒性通路中，受上述miRNA调控的基因数量最多。其余富集通路则涵盖多种恶性肿瘤相关信号通路及其他信号通路。<b>结论：</b>本研究筛选得到的miRNA荟萃特征可作为区分口腔癌组织与正常非癌组织的潜在生物标志物组合。未来需开展进一步机制研究，以验证并阐明这些表达失调的miRNA在口腔癌发生发展中的具体作用。