Abstract
Nasopharyngeal carcinoma is a metastatic malignant tumor originating from nasopharyngeal epithelium. Lacking or nonspecific symptoms of patients with early stage nasopharyngeal carcinoma have significantly reduced the accuracy of diagnosing and predicting nasopharyngeal carcinoma development. This study aimed to identify gene signatures of nasopharyngeal carcinoma and uncover potential mechanisms. Two gene expression profiles (GSE12452 and GSE13597) containing 56 nasopharyngeal carcinoma samples and 13 normal control samples were analyzed to identify the differentially expressed genes. In total, 179 up-regulated genes and 238 down-regulated genes were identified. Functional and pathway enrichment analysis showed that up-regulated genes were significantly involved in cell cycle, oocyte meiosis, DNA replication and p53 signaling pathway, while down-regulated genes were enriched in Huntington's disease,metabolic pathways. Subsequently, the top 10 hub genes, TOP2A (topoisomerase (DNA) II alpha), CDK1 (cyclin-dependent kinase 1), CCNB1 (cyclin B1), PCNA (proliferating cell nuclear antigen), MAD2L1 (mitotic arrest deficient 2 like 1), BUB1 (budding uninhibited by benzimidazoles 1 homolog), CCNB2 (cyclin B2), AURKA (aurora kinase A), CCNA2 (cyclin A2), CDC6 (cell division cycle 6 homolog), were identified from protein-protein interaction network. Furthermore, Module analysis revealed that the ten hub genes except TOP2A were belonged to module 1, indicating the upregulation of these hub genes associated molecular pathways in nasopharyngeal carcinoma might activate nasopharyngeal carcinoma pathogenesis. In conclusion, this study indicated that the identified differentially expressed genes and hub genes enrich our understanding of the molecular mechanisms of nasopharyngeal carcinoma, which could eventually translate into additional biomarkers to facilitate the early diagnosis and therapeutic approaches.
Highlights
Nasopharyngeal carcinoma (NPC) is the most common squamous cell carcinoma arising from nasopharynx
The raw data file of GSE12452 and GSE13597 were uploaded to GEO2R to screen differentially expressed genes (DGEs) between nasopharyngeal carcinoma and normal samples
417 differentially expressed genes (DEGs) lists were identified using FunRich_V3 software [8], consisting of 179 up-regulated genes and 238 down-regulated genes in nasopharyngeal carcinoma samples compared to normal nasopharyngeal tissue samples
Summary
Nasopharyngeal carcinoma (NPC) is the most common squamous cell carcinoma arising from nasopharynx. Clinically NPC is often diagnosed in a late stage and has a relatively poor survival rate after diagnosis [3]. The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high-risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development [3]. Increasing evidence proves that polygenes and cell pathways are involved in the development and progression of NPC [5]. The precise molecular mechanisms for the development of nasopharyngeal cancer are unknown, which limits the potential for early diagnosis and treatment of NPC. It is crucial to investigate the molecular mechanisms in nasopharyngeal carcinoma progression and discover additional biomarkers to facilitate the early diagnosis and curative treatment
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