Abstract Number: OC 30.2
Meeting: ISTH 2021 Congress
Background: Venous thromboembolism (VTE) is a frequent complication in cancer patients. In patients with pancreatic cancer, VTE risk is much higher than in other cancer types, implying that tumor-intrinsic features drive hypercoagulability. It remains to be investigated whether tumor gene expression in these patients is associated with development of VTE.
Aims: To evaluate the association between tumor gene expression and VTE in patients with pancreatic cancer.
Methods: RNA-sequencing was performed on resected tumor material from 213 patients with pancreatic cancer. Data on thromboembolic events during a 6-month follow-up period after surgery were collected retrospectively. The primary outcome was proximal deep vein thrombosis (DVT) of the leg, and/or pulmonary embolism (PE). Secondary outcomes were all other venous thromboembolic events. Protein coding genes with an adjusted P-value <0.05 after multiple testing correction (false discovery rate) were considered statistically significant. KEGG pathway analysis was performed to identify pathways associated with VTE.
Results: In 184 (86%) out of 213 patients, complete 6-months follow-up data could be obtained. Ninety-five (52%) were male and the median age was 65 years (SD 9.3). Thirty-two patients had recurrence (17.4%) within 6 months and 25 (14%) patients died. 16 patients developed a VTE of which 4 (25%) had recurrent disease. Seven patients (4%) developed DVT and/or PE and nine patients (5%) had another venous thromboembolic event. RNA-sequencing analysis yielded 9 genes significantly associated with the primary outcome and 31 genes with the secondary outcome (Table 1). In both outcomes, G-protein-coupled receptors from the olfactory receptor gene family were significantly associated with VTE. KEGG pathway analysis identified the olfactory-transduction pathway to be associated with VTE.
|Primary outcome||Secondary outcome|
|Gene symbol||Fold Change (log2)||Function||Adjusted P-value||Gene symbol||Fold Change (log2)||Function||Adjusted P-value|
|OR4D6||1.14||Transmembrane signaling receptor activity||4.68e-7||TAS2R7||1.17||membrane, signal transduction||0.0000105|
|SCP2D1||1.17||Sterol binding||0.0000222||CLVS2||5.17||lipid binding||0.0000133|
|OR1N1||1.34||Transmembrane signaling receptor activity||0.00169||MYO18B||4.98||nucleotide binding||0.000253|
|CYP2F1||4.85||Monooxygenase activity||0.00493||SLC7A13||2.36||transmembrane transporter activity||0.00027|
|IFNA6||1.23||Cytokine activity||0.00566||DPPA2||3.05||chromatin binding||0.00055|
|SPTA1||5.75||Actin binding||0.00983||PRLHR||2.19||membrane, signal transduction||0.000569|
|NMKR2||1.8||nucleotide binding||0.022||C5ORF38||2.81||extracellular region||0.00203|
|FOXR2||1.19||DNA-binding transcription factor activity||0.027||PPP4R3C||1.78||modulates glycogen metabolism||0.00228|
Conclusions: Multiple genes from the olfactory receptor gene family were associated with VTE in patients with pancreatic cancer. These data provide a path to further elucidate the pathophysiology of cancer-associated VTE and predict VTE risk based on tumor gene expression.
To cite this abstract in AMA style:Bosch F, van Dijk F, Briedé S, Groen J, Hanna-Sawires R, Klok F, Kaasjager H, Brosens L, Molenaar I, Bonsing B, Mieog J, Besselink M, Busch O, Verheij J, Farina-Sarasqueta A, Wilmink J, Bijlsma M, Versteeg H, van Es N, Buijs JT. Tumor Gene Expression Associates with Venous Thromboembolism in Patients with Pancreatic Cancer [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/tumor-gene-expression-associates-with-venous-thromboembolism-in-patients-with-pancreatic-cancer/. Accessed December 6, 2023.
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