期刊
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
卷 41, 期 5, 页码 414-428出版社
OXFORD UNIV PRESS
DOI: 10.1093/abbs/gmp025
关键词
signaling pathway; nasopharyngeal carcinoma; gene set enrichment analysis; cDNA microarray; tissue microarray; Epstein-Barr virus
资金
- National Key Project of Scientific Research Program [2006CB910502, 2006CB910504]
- National Natural Science Foundation of China [30700469, 30770825, 30871282, 30871356]
- Foundation for the Author of National Excellent Doctoral Dissertation of the PR China [200559]
- National '863' High Technology Program of China [2007AA02Z170]
- Hunan Provincial Natural Science Foundation of China [06JJ20013]
Previous studies have revealed that Epstein-Barr virus (EBV) was closely associated with nasopharyngeal carcinoma (NPC). This study aimed to characterize the global pathways affected in the EBV-associated NPC. Combined with microdissection, gene expression profiles in 22 NPCs and 10 non-tumor nasopharyngeal epithelial (NPE) tissue samples were analyzed. All NPC specimens served in the microarray analysis were positive for EBV, as judged by identification of the expression of EBV nuclear antigen 1 (EBNA1). Through gene set enrichment analysis (GSEA), we found that cell cycle pathway was the most disregulated pathway in NPC (P = 0.000, false discovery rate q-value = 0.007), which included some aberrant expressed components. We first found that overexpression of CDK4, cyclin D1, and Rb proteins, and loss of expression of proteins p16, p27, and p19 were statistically significant in NPC tissues compared with non-cancerous NPE (P < 0.05) by real-time RT-PCR and tissue microarray. EBV-encoded small RNA-1 (EBER-1) hybridization signals in the NPC showed significant associations with the overexpression of Rb (P = 0.000), cyclin D1 (P = 0.000), CDK4 (P = 0.000), and the loss of expression of p16 proteins (P = 0.039). In the final logistic regression analysis model, EBER-1 and abnormal expression of p16, Rb, cyclin D1, and E2F6 were independent contributions to nasopharyngeal carcinogenesis. Through survival analysis, only cyclin D1 could predict the prognosis of NPC patients. These results suggested that cell cycle pathway was the most disregulated pathway in the EBV-associated NPC, and EBER-1 was closely associated with p16, CDK4, cyclin D1, and Rb. cyclin D1 could be the prognosis biomarker for NPC.
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