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.
Division of Cardiovascular Sciences, Centro de Investigación Médica Aplicada, Pamplona, Spain.
Ramón
R
Montes
Bioinformatics Unit, Centro de Investigación Médica Aplicada, Pamplona, Spain.
Elisabet
E
Guruceaga
Hematology Service, Hospital Clínico Universitario, Salamanca, Spain.
José R
JR
González-Porras
Department of Haemotherapy and Haemostasis, Hospital Clinic, Barcelona, Spain.
Joan C
JC
Reverter
Hematology Service, Hospital General Universitario de Alicante, Alicante, Spain.
Pascual
P
Marco
Thrombosis and Haemostasis Unit, Hospital Universitari Bellvitge, Hospitalet de Llobregat, Pamplona, Spain.
Elena
E
Pina
Hematology Service, University Clinic of Navarra, Pamplona, Spain.
José A
JA
Páramo
Division of Cardiovascular Sciences, Centro de Investigación Médica Aplicada, Pamplona, Spain.
José
J
Hermida
Hematology Service, University Clinic of Navarra, Pamplona, Spain.
Ramón
R
Lecumberri
D000328:Adult; D015415:Biomarkers; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D059467:Transcriptome; D020246:Venous Thrombosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*
D015415:Biomarkers
ACSF2; deep venous thrombosis; gene expression profiling; recurrence