Analysis of pigmented villonodular synovitis with genome‐wide complementary DNA microarray and tissue array technology reveals insight into potential novel therapeutic approaches

Abstract

ObjectiveTo characterize the gene expression profile and determine potential diagnostic markers and therapeutic targets in pigmented villonodular synovitis (PVNS).MethodsGene 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).ResultsThe 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 ≥1.5; Q ≤ 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).ConclusionThe 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.

Multi‐lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells ‐ pathological implication

“…These genes have been shown to be crucial in the vessel formation and tumor angiogenesis . However, they were quite different from those reported in the study of Finis et al, where genes differentially expressed in PVNS compared to OA and RA, including ALOX5AP, ATP6V1B2, CD53, CHI3L1, CTSL, CXCR4, HSPA8, HSPCA, LAPTM5, MMP9, MOAP1, and SPP1, were mainly involved in apoptosis regulation, matrix degradation, and inflammation . We believed that this is because those previous studies used pathological samples (for example: RA, OA or tumors) and tissues, which contained multiple cell types, for the analysis of gene profiling.…”

“…In one previous study, Finis et al concluded that PVNS tissue had clearly distinct gene expression profile from those in rheumatoid arthritis (RA) and osteoarthritis (OA), and these genes in PVNS were mainly involved in apoptosis regulation, matrix degradation, and inflammation . Additionally, up‐regulation of the colony stimulating factor 1 (CSF1) has been reported in PVNS .…”

Outcomes of Diffuse-Type Pigmented Villonodular Synovitis (PVNS) after Open Total Synovectomy

“…2,[5][6][7]11,[13][14][15]17,19,21,22) Although the pathogenesis of PVNS is still unclear, Bertoni et al 23) reported characteristics of a malignant form PVNS in 8 cases, and Oda et al 24) published 25) described that PVNS had a decreased apoptotic cell cycle, like other malignancies. Layfield et al 26) found trisomies in the fifth and seventh chromosomes within tissue of PVNS.…”

Real-Time PCR Data Processing Shown by the Analysis of Colorectal Specific Candidate Genes, ERCC1, RRM1 and TS in Relation to β2M as Endogenous Control

“…The ΔΔC T value was calculated by subtracting the ΔC T value for the normal cells from the ΔC T value of the tumor cells [13]. Fold of enrichment values was determined according to the ratio 2 −ΔΔCT (see example).…”