Abstract
BackgroundNasopharyngeal carcinoma (NPC) is an epithelial malignancy with high morbidity rates in the east and southeast Asia. The molecular mechanisms of NPC remain largely unknown. We explored the pathogenesis, potential biomarkers, and prognostic indicators of NPC.MethodsWe analyzed mRNAs, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) in the whole transcriptome sequencing dataset of our hospital (five normal tissues vs. five NPC tissues) and six microarray datasets (62 normal tissues vs. 334 NPC tissues) downloaded from the Gene Expression Omnibus (GSE12452, GSE13597, GSE95166, GSE126683, and GSE70970, GSE43039). Differential expression analyses, gene ontology (GO) enrichment, kyoto encyclopedia of genes and genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted. The lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed using the miRanda and TargetScan database, and a protein–protein interaction (PPI) network of differentially expressed genes (DEGs) was built using Search Tool for the Retrieval of Interacting Genes (STRING) software. Hub genes were identified using Molecular Complex Detection (MCODE), NetworkAnalyzer, and CytoHubba.ResultsWe identified 61 mRNAs, 14miRNAs, and 10 lncRNAs as shared DEGs related to NPC in seven datasets. Changes in NPC were enriched in the chromosomal region, sister chromatid segregation, and nuclear chromosome segregation. GSEA indicated that the mitogen-activated protein kinase (MAPK) pathway, phosphatidylinositol-3 OH kinase/protein kinase B (PI3K-Akt) pathway, apoptotic pathway, and tumor necrosis factor (TNF) were involved in the initiation and development of NPC. Finally, 20 hub genes were screened out via the PPI network.ConclusionsSeveral DEGs and their biological processes, pathways, and interrelations were found in our current study by bioinformatics analyses. Our findings may offer insights into the biological mechanisms underlying NPC and identify potential therapeutic targets for NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with high morbidity rates in the east and southeast Asia
61 differentially expressed genes (DEGs) were shared among the three mRNA datasets (Fig. 2d), 10 differentially expressed long non-coding RNAs (lncRNAs) (DElncRNAs) were shared among the three lncRNA datasets (Fig. 2h), and 14 differentially expressed miRNAs (DEmiRNAs) were shared among the two miRNA datasets (Fig. 2k)
Those DEGs may provide new insight into the biological mechanisms of NPC and serve as Construction of the competing endogenous RNA (ceRNA) network To explore the role of miRNAs and corresponding target mRNAs, as well as corresponding lncRNAs in NPC, we predicted the target mRNAs of the DEmiRNAs, and lncRNAs that may have interrelations with miRNAs
Summary
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with high morbidity rates in the east and southeast Asia. Potential biomarkers, and prognostic indicators of NPC. The incidence of NPC is geographically imbalanced, with new cases mainly concentrated in east and southeast Asia, especially in South China [3, 4]. The estimated age-standardized incidence rate of NPC is 3.0 per 100,000 in China and only 0.47 per 100,000 in North America [1, 5]. In the early stages of NPC, the main pathogenesis is related to EBV infection [7]. Despite the great advances in medical technology in recent years, such as the application of intensity-modulated radiotherapy and optimized chemotherapy strategies, the detection and treatment of NPC remain challenging [9]. Noninvasive, cancer-specific biomarkers for early diagnosis and precision treatment are urgently required
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