Tian Huan, Chen Shicai, Zhang Caiyun, Li Meng, Zheng Hongliang
Department of Otolaryngology‑Head and Neck Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1039-1046. doi: 10.3892/mmr.2017.6696. Epub 2017 Jun 6.
The present study was performed to identify the dysregulated microRNAs (miRNAs/miRs) and mRNAs, and enriched pathways involved in nasopharyngeal carcinoma (NPC) through the establishment of an miRNA‑mRNA‑pathways network. mRNA and miRNA expression profiles were collected from the European Molecular Biology Laboratory‑European Bioinformatics Institute. Differentially expressed genes and differentially expressed miRNA were selectively screened using the metaDE package. Following prediction of the risk genes and pathway pairs involved in NPC, an miRNA‑mRNA‑pathway network was constructed by merging the miRNA‑mRNA pairs, the mRNA‑pathway pairs and the mRNA‑mRNA pairs. The miRNA and mRNA biomarkers, as well as the functional pathway pairs, were identified in the network analysis, based on the topological properties of nodes in the network. Additionally, 10‑fold cross‑validation was performed to evaluate the performance of the selected risk genes and their corresponding miRNA in NPC by calculating the area under the curve (AUC). In total, 99 upregulated and 841 downregulated genes, and 192 upregulated and 26 downregulated miRNAs were identified. The miRNA‑mRNA‑pathway network was established using 403 miRNA‑mRNA pairs, including 40 miRNAs and 302 risk genes, as well as 22 prominent pathway pairs. Network analysis demonstrated that v‑myc avian myelocytomatosis viral oncogene homolog (MYC) and hsa‑miR‑423‑5p were the mRNA and miRNA signatures for NPC, respectively. The AUC of these biomarkers for NPC was 0.7568 and 0.7798, respectively. Additionally, the focal adhesion pair pathway in cancer was identified to be associated with NPC. MYC and hsa‑miR‑423‑5p have been identified to be critical biomarkers in NPC as revealed by miRNA‑mRNA‑pathway network integrated analysis, suggesting a direction for further research into the diagnosis and treatment of NPC.
本研究旨在通过构建miRNA-mRNA-通路网络,鉴定鼻咽癌(NPC)中失调的微小RNA(miRNA/miR)和信使核糖核酸(mRNA),以及富集的通路。从欧洲分子生物学实验室-欧洲生物信息学研究所收集mRNA和miRNA表达谱。使用metaDE软件包选择性筛选差异表达基因和差异表达miRNA。在预测与NPC相关的风险基因和通路对后,通过合并miRNA-mRNA对、mRNA-通路对和mRNA-mRNA对构建miRNA-mRNA-通路网络。基于网络中节点的拓扑特性,在网络分析中鉴定了miRNA和mRNA生物标志物以及功能通路对。此外,通过计算曲线下面积(AUC)进行10倍交叉验证,以评估所选风险基因及其相应miRNA在NPC中的性能。总共鉴定出99个上调基因和841个下调基因,以及192个上调miRNA和26个下调miRNA。使用403个miRNA-mRNA对建立了miRNA-mRNA-通路网络,其中包括40个miRNA和302个风险基因,以及22个显著的通路对。网络分析表明,v-myc禽骨髓细胞瘤病毒癌基因同源物(MYC)和hsa-miR-423-5p分别是NPC的mRNA和miRNA特征。这些生物标志物对NPC的AUC分别为0.7568和0.7798。此外,癌症中的粘着斑对通路被确定与NPC相关。通过miRNA-mRNA-通路网络综合分析发现,MYC和hsa-miR-423-5p是NPC中的关键生物标志物,为NPC的进一步诊断和治疗研究提供了方向。