Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer.
OBJECTIVE
Gastric cancer is usually diagnosed at later stages (stages III and IV) in China, and the overall 5-year survival rate is low at 40%. Metastases are responsible for the majority of cancer fatalities. The molecular mechanisms governing metastasis are poorly understood.


METHODS
We have analyzed gene expression data based on gene interaction networks and molecular pathways rather than separate genes utilizing hierarchical cluster analysis, Gene ontology analysis and pathway analysis.


RESULTS
We have analyzed gene expression data from advanced gastric cancer tissues, corresponding adjacent noncancerous gastric tissues and its peritonium metastasis. Our studies indicated that metastatic tumor was related to changes in apoptosis pathway and proteasome degradation pathway, TRAF2 and IRF3 are up-regulated in apoptosis pathway, NEDD4 and UBE1 are up-regulated in proteasome degradation pathway.


CONCLUSIONS
The advent of high-throughput investigation of gene using Microarray technology, a systems approach relying on groups of interacting genes is essential for understanding the processes of cancer. We have identified apoptosis pathway and proteasome degradation pathway associated with metastasis.
Wang
Yuan-Yu
YY
Department of Surgery, Zhejiang Provincial People's Hospital, 310014 Hangzhou, Zhejiang, People's Republic of China.
Ye
Zai-Yuan
ZY
Zhao
Zhong-Sheng
ZS
Tao
Hou-Quan
HQ
Li
Shu-Guang
SG
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D049490:Systems Biology / Q000379:methods
D014408:Biomarkers, Tumor