mRNA profiling of the cancer degradome in oesophago-gastric adenocarcinoma.
BACKGROUND
Degradation of the extracellular matrix is fundamental to tumour development, invasion and metastasis. Several protease families have been implicated in the development of a broad range of tumour types, including oesophago-gastric (OG) adenocarcinoma. The aim of this study was to analyse the expression levels of all core members of the cancer degradome in OG adenocarcinoma and to investigate the relationship between expression levels and tumour/patient variables associated with poor prognosis.


METHODS
Comprehensive expression profiling of the protease families (matrix metalloproteinases (MMPs), members of the ADAM metalloproteinase-disintegrin family (ADAMs)), their inhibitors (tissue inhibitors of metalloproteinase), and molecules involved in the c-Met signalling pathway, was performed using quantitative real-time reverse transcription polymerase chain reaction in a cohort of matched malignant and benign peri-tumoural OG tissue (n=25 patients). Data were analysed with respect to clinico-pathological variables (tumour stage and grade, age, sex and pre-operative plasma C-reactive protein level).


RESULTS
Gene expression of MMP1, 3, 7, 9, 10, 11, 12, 16 and 24 was upregulated by factors >4-fold in OG adenocarcinoma samples compared with matched benign tissue (P<0.01). Expression of ADAM8 and ADAM15 correlated significantly with tumour stage (P=0.048 and P=0.044), and ADAM12 expression correlated with tumour grade (P=0.011).


CONCLUSIONS
This study represents the first comprehensive quantitative analysis of the expression of proteases and their inhibitors in human OG adenocarcinoma. These findings implicate elevated ADAM8, 12 and 15 mRNA expression as potential prognostic molecular markers.
Tissue Injury and Repair Group, Clinical and Surgical Sciences, University of Edinburgh-MRC Centre for Regenerative Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK.
J P
JP
Baren
G D
GD
Stewart
A
A
Stokes
K
K
Gray
C J
CJ
Pennington
R
R
O'Neill
D A C
DA
Deans
S
S
Paterson-Brown
A C P
AC
Riddick
D R
DR
Edwards
K C H
KC
Fearon
J A
JA
Ross
R J E
RJ
Skipworth
D051722:ADAM Proteins / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D002097:C-Reactive Protein; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases