Over-expression of Ephb4 is associated with carcinogenesis of gastric cancer.
BACKGROUND
Gastric cancer is one of the most frequently diagnosed malignancies in the world. The gene expression profile and molecular grouping of gastric cancer has been a challenging task due to its inherent complexity and variation among individuals.


OBJECTIVE
To determine the molecular mechanism associated with gastric carcinogenesis.


METHODS
We analyzed the gene expression profiles of 20 cancerous tissues and their tumor-adjacent tissue from patients with gastric cancer by using a 14 K cDNA microarray. The differentially expressed genes and their products were verified by semiquantitative reverse transcription PCR (RT-PCR), western blotting and immunohistochemistry of gastric cancer and normal tissue samples.


RESULTS
A total of 69 genes were found to be differentially regulated in the cancerous tissue. Among them, genes such as CDH17, ETV4, S100A6, S100A11, Ephb4, and KLK10 were confirmed by RT-PCR to be up-regulated, while genes such as NK4 and PPP2R1B were down-regulated. Western blotting and immunohistochemistry indicated that Ephb4 was over-expressed and localized to the cytoplasm of gastric cancer cells. Moreover, Ephb4 protein was observed as being significantly related to tumor size and pN category (p = 0.001 and 0.007, respectively).


CONCLUSIONS
These newly identified genes might provide a valuable resource for understanding the molecular mechanism associated with the carcinogenesis of gastric cancer and for finding potential diagnostic markers of gastric cancer.
Li
M
M
Department of Medical Oncology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning Province, China.
Zhao
Z W
ZW
Zhang
Y
Y
Xin
Y
Y
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054648:Protein Phosphatase 2 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D036224:Receptor, EphB4 / Q000378:metabolism*; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D017500:Adenovirus E1A Proteins; C490584:CDH17 protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; C079853:ETV4 protein, human; C066855:HGF protein, human; C432785:PPP2R1B protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human; C072337:S100A11 protein, human; D017228:Hepatocyte Growth Factor; D036224:Receptor, EphB4; D054648:Protein Phosphatase 2; C100936:KLK10 protein, human; D007610:Kallikreins