Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China.
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.


CONCLUSIONS
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.
Cancer Research Institute of Southern Medical University, Key Lab for Transcriptomics and Proteomics of Human Fatal Diseases Supported by Ministry of Education and Guangdong Province, 510515, PR China. fangweiyi1975@yahoo.com.cn
Weiyi
W
Fang
Xin
X
Li
Qingping
Q
Jiang
Zhen
Z
Liu
Huiling
H
Yang
Shuang
S
Wang
Siming
S
Xie
Qiuzhen
Q
Liu
Tengfei
T
Liu
Jing
J
Huang
Weibing
W
Xie
Zuguo
Z
Li
Yingdong
Y
Zhao
Ena
E
Wang
Francesco M
FM
Marincola
Kaitai
K
Yao
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002681:China; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology
D014408:Biomarkers, Tumor