Analysis of pigmented villonodular synovitis with genome-wide complementary DNA microarray and tissue array technology reveals insight into potential novel therapeutic approaches.
OBJECTIVE
To characterize the gene expression profile and determine potential diagnostic markers and therapeutic targets in pigmented villonodular synovitis (PVNS).


METHODS
Gene expression patterns in 11 patients with PVNS, 18 patients with rheumatoid arthritis (RA), and 19 patients with osteoarthritis (OA) were investigated using genome-wide complementary DNA microarrays. Validation of differentially expressed genes was performed by real-time quantitative polymerase chain reaction and immunohistochemical analysis on tissue arrays (80 patients with PVNS, 51 patients with RA, and 20 patients with OA).


RESULTS
The gene expression profile in PVNS was clearly distinct from those in RA and OA. One hundred forty-one up-regulated genes and 47 down-regulated genes were found in PVNS compared with RA, and 153 up-regulated genes and 89 down-regulated genes were found in PVNS compared with OA (fold change > or = 1.5; Q < or = 0.001). Genes differentially expressed in PVNS were involved in apoptosis regulation, matrix degradation, and inflammation (ALOX5AP, ATP6V1B2, CD53, CHI3L1, CTSL, CXCR4, HSPA8, HSPCA, LAPTM5, MMP9, MOAP1, and SPP1).


CONCLUSIONS
The gene expression signature in PVNS is similar to that of activated macrophages and is consistent with the local destructive course of the disease. The gene and protein expression patterns suggest that the ongoing proliferation in PVNS is sustained by apoptosis resistance. This result suggests the possibility of a potential novel therapeutic intervention against PVNS.
Finis
Katharina
K
German Cancer Research Center, Heidelberg, Germany.
Sültmann
Holger
H
Ruschhaupt
Markus
M
Buness
Andreas
A
Helmchen
Birgit
B
Kuner
Ruprecht
R
Gross
Marie-Luise
ML
Fink
Bernd
B
Schirmacher
Peter
P
Poustka
Annemarie
A
Berger
Irina
I
D001172:Arthritis, Rheumatoid / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics; D013586:Synovitis, Pigmented Villonodular / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D046888:Tissue Array Analysis; D015854:Up-Regulation
D018076:DNA, Complementary