Quantitative gene expression in Budd-Chiari syndrome: a molecular approach to the pathogenesis of the disease.
BACKGROUND
Budd-Chiari syndrome (BCS) is associated with parenchymal changes leading to major architecture remodelling. In order to gain further insight into the pathogenesis of BCS, we investigated expression of a set of genes involved in the course of chronic liver diseases.


METHODS
Quantitative expression of 35 selected genes involved in extracellular matrix regulation, growth factors, and angiogenesis was investigated in 13 cases of BCS and compared with 10 normal livers and 13 cirrhosis cases by real time reverse transcription-polymerase chain reaction. Differential gene expression was considered significant for genes showing at least a twofold variation, with p < 0.05.


RESULTS
Expression of 14 genes was significantly increased in BCS versus normal liver, with the highest increase in superior cervical ganglion 10 (SCG10) gene. BCS cases were classified according to their evolution and morphological pattern as either acute or chronic in six and seven cases, respectively. Unsupervised hierarchical clustering of acute and chronic BCS cases on the basis of similarity in gene expression pattern led to distinction between the two groups. Expression of three genes was significantly different in acute versus chronic BCS (increase in matrix metalloproteinase 7 and SCG10, decrease in thrombospondin-1 for chronic BCS). Seventeen and 10 genes, mainly involved in extracellular matrix and vascular remodelling, were significantly deregulated in acute BCS versus normal liver and cirrhosis, respectively.


CONCLUSIONS
These results show that BCS cases display a specific gene expression profile that is different from that of normal liver and cirrhosis; the molecular configuration of BCS can be readily distinguished by its evolution and morphological pattern.
Paradis
V
V
Service d'Anatomie Pathologique, Hôpital Beaujon, 110 bd du général Leclerc, 92118 Clichy Cedex, France. vparadis@teaser.fr
Bièche
I
I
Dargère
D
D
Cazals-Hatem
D
D
Laurendeau
I
I
Saada
V
V
Belghiti
J
J
Bezeaud
A
A
Vidaud
M
M
Bedossa
P
P
Valla
D-C
DC
D000208:Acute Disease; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D006502:Budd-Chiari Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D043925:Angiogenesis Inducing Agents; D006133:Growth Substances