Identification of new markers of recurrence in patients with unprovoked deep vein thrombosis by gene expression profiling: the retro study.

OBJECTIVE: The aim of this study was to assess differences in the gene expression profile of peripheral blood cells between patients with early recurrent thrombosis vs. patients without recurrent events after withdrawal of anticoagulant therapy for a first episode of unprovoked deep vein thrombosis (uDVT), to identify novel predictors of recurrence.

METHODS: In the discovery population (N = 32), a microarray RNA assay followed by RT-PCR confirmation were performed. In the validation population (N = 44) a multiple RT-PCR-based strategy was applied to assess genes differentially expressed in the discovery population.

RESULTS: The sex-adjusted Linear Model for Microarray Data analysis showed 102 genes differentially expressed (P < 0.01) in the discovery population. Nineteen of them underwent further confirmation in the validation population. The gene encoding for Acyl-CoA Synthetase Family Member 2 (ACSF2) was underexpressed in recurrent DVT patients in both, the discovery (P = 0.007) and validation populations (P = 0.004). In the receiver operator characteristic (ROC) analysis, the areas under the curve of ACSF2 expression were 0.77 and 0.80, respectively.

CONCLUSIONS: For the first time an association between ACSF2 expression and the risk of recurrent DVT is suggested. Should this association be confirmed in larger prospective studies, ACSF2 could become useful for the selection of patients requiring extended anticoagulant therapy.