Abstract Number: OC 30.2
Meeting: ISTH 2021 Congress
Theme: Venous Thromboembolism » Cancer Associated Thrombosis
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 |
| TDRD3 | 1.22 | Chromatin binding | 0.018 | THEG | 1.86 | spermatogenesis | 0.00124 |
| 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 |
Top genes associated with venous thromboembolism in patients with pancreatic ductal adenocarcinoma
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.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/tumor-gene-expression-associates-with-venous-thromboembolism-in-patients-with-pancreatic-cancer/