PGK1 a potential marker for peritoneal dissemination in gastric cancer.
OBJECTIVE
Peritoneal carcinomatosis, which is caused by the dissemination of cancer cells into the abdominal cavity is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. The mechanisms that mediate peritoneal carcinomatosis in diffuse primary gastric tumours require definition.


METHODS
We therefore compared the gene expression profile in diffuse primary gastric cancer patients with and without peritoneal carcinomatosis (n=13). Human specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Differentially expressed genes of interest were further evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).


RESULTS
The results reveal a significant overexpression of phosphoglycerate kinase 1 (PGK1), the chemokine CXCR4 and its ligand CXCL12 in specimens from diffuse gastric cancer patients with peritoneal carcinomatosis. Overexpression of PGK1 is known to increase the expression of CXCR4. CXCR4 on its part can increase CXCL12 expression. Elevated levels of CXCR4 and CXCL12 are associated with an increase in the metastatic rate and play an important role in the metastatic homing of malignant cells.


CONCLUSIONS
The overexpression of PGK1 and its signalling targets may be a expression-pathway in diffuse primary gastric carcinomas promoting peritoneal dissemination and may function as prognostic markers and/or be potential therapeutic targets to prevent the migration of gastric carcinoma cells into the peritoneum.
Zieker
Derek
D
Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, Tuebingen, Germany. derek.zieker@med.uni-tuebingen.de
Königsrainer
Ingmar
I
Traub
Frank
F
Nieselt
Kay
K
Knapp
Bettina
B
Schillinger
Christian
C
Stirnkorb
Christian
C
Fend
Falko
F
Northoff
Hinnak
H
Kupka
Susan
S
Brücher
Björn L D M
BL
Königsrainer
Alfred
A
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary*; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D010735:Phosphoglycerate Kinase