Author:
Fang Weiyi,Li Xin,Jiang Qingping,Liu Zhen,Yang Huiling,Wang Shuang,Xie Siming,Liu Qiuzhen,Liu Tengfei,Huang Jing,Xie Weibing,Li Zuguo,Zhao Yingdong,Wang Ena,Marincola Francesco M,Yao Kaitai
Abstract
Abstract
Background
The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated.
Methods
Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry.
Results
Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation.
Conclusion
This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference33 articles.
1. Sriuranpong V, Mutirangura A, Gillespie JW, Patel V, Amornphimoltham P, Molinolo AA, Kerekhanjanarong V, Supanakorn S, Supiyaphun P, Rangdaeng S, Voravud N, Gutkind JS: Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays. Clin Cancer Res. 2004, 10 (15): 4944-4958. 10.1158/1078-0432.CCR-03-0757.
2. Li RP, Shao JY, Deng L, Zeng MS, Song LB, Li MZ, Wu QL: [Identification of differentially expressed genes in primary cultured nasopharyngeal carcinoma cells by cDNA microarray]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2007, 27 (8): 1156-1160.
3. Zhou L, Jiang W, Ren C, Yin Z, Feng X, Liu W, Tao Q, Yao K: Frequent hypermethylation of RASSF1A and TSLC1, and high viral load of Epstein-Barr Virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues. Neoplasia. 2005, 7 (9): 809-815. 10.1593/neo.05217.
4. Qiu GH, Tan LK, Loh KS, Lim CY, Srivastava G, Tsai ST, Tsao SW, Tao Q: The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene. 2004, 23 (27): 4793-4806. 10.1038/sj.onc.1207632.
5. Yan W, Song L, Wei W, Li A, Liu J, Fang Y: Chromosomal abnormalities associated with neck nodal metastasis in nasopharyngeal carcinoma. Tumour Biol. 2005, 26 (6): 306-312. 10.1159/000089289.