Meta-analysis of nasopharyngeal carcinoma microarray data explores mechanism of EBV-regulated neoplastic transformation.
BACKGROUND
Epstein-Barr virus (EBV) presumably plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC), but the molecular mechanism of EBV-dependent neoplastic transformation is not well understood. The combination of bioinformatics with evidences from biological experiments paved a new way to gain more insights into the molecular mechanism of cancer.


RESULTS
We profiled gene expression using a meta-analysis approach. Two sets of meta-genes were obtained. Meta-A genes were identified by finding those commonly activated/deactivated upon EBV infection/reactivation. These genes could be key players for pathways de-regulated by EBV during latent infection and lytic proliferation. Meta-B genes were obtained from differential genes commonly expressed in NPC and PEL (primary effusion lymphoma). We then integrated meta-A, meta-B and associated factors into an interaction network using acquired information. Our analysis suggests that NPC transformation depends on timely regulation of DEK, CDK inhibitor(s), p53, RB and several transcriptional cascades, interconnected by E2F, AP-1, NF-kappaB, STAT3 among others during latent and lytic cycles.


CONCLUSIONS
In conclusion, our meta-analysis strategy re-analyzed EBV-related tumor data sets and identified sets of meta-genes possibly involved in maintaining latent or switching to lytic cycles of EBV in NPC. The results of this analysis may shed new lights to further our understanding of the EBV-led neoplastic transformation.
Chen
Xia
X
Institute of Genetic Engineering, Southern Medical University, Guangzhou, PR China. chenxiayi@126.com
Liang
Shuang
S
Zheng
WenLing
W
Liao
ZhiJun
Z
Shang
Tao
T
Ma
WenLi
W
D001665:Binding Sites / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral; D030561:Databases, Nucleic Acid; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D004854:Herpesvirus 4, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D017735:Virus Latency
D014157:Transcription Factors