Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism [Set1]

Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. We studied 134 patients with VTE separated into 3 groups: (1) low-risk patients had 1 provoked VTE; (2) moderate-risk patients had no more than 1 unprovoked VTE; (3) high-risk patients had 2 unprovoked VTE. 44 individuals with no history of VTE were enrolled as healthy controls. Consented individuals were enrolled at 4 medical centers in the US. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Using class prediction analysis, we distinguished high-risk patients from healthy controls with good receiver operating curve characteristics (AUC=0.88). We also distinguished high-risk from low-risk individuals, moderate-risk individuals from healthy controls, and low-risk individuals from healthy controls with AUCs of 0.72, 0.77 and 0.72, respectively. Using differential expression analysis, we identified genes relevant to coagulation, immune response and vascular biology, such as SELP and CD46, which were differentially expressed in at least two comparisons. Neither approach distinguished the moderate-risk patients from the high-risk or low-risk groups. Gene expression profiles may provide insights into biological mechanisms associated with patients at risk for recurrent VTE. Prospective studies are needed to validate these findings.

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Lewis DA, Suchindran S, Beckman MG, Hooper WC, Grant AM, Heit JA, Manco-Johnson M, Moll S, Philipp CS, Kenney K, De Staercke C, Pyle ME, Chi JT, Ortel TL