Genes associated with venous thromboembolism in colorectal cancer patients

• Published in: Journal of thrombosis and haemostasis 2018-02, Vol.16 (2), p.293-302
• Main Authors: Ünlü, B., Es, N., Arindrarto, W., Kiełbasa, S. M., Mei, H., Westerga, J., Middeldorp, S., Kuppen, P. J. K., Otten, J.M.M.B., Cannegieter, S., Versteeg, H. H.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Blood Coagulation - genetics; Case-Control Studies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - blood; Colorectal Neoplasms - complications; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Degradation products; Female; Fibrin; Gene expression; Gene Expression Profiling; Gene Regulatory Networks; Genetic Predisposition to Disease; homocysteine; Humans; Inflammation; Male; Methionine; Middle Aged; Morbidity; Phenotype; Proof of Concept Study; Risk Assessment; Risk Factors; RNA sequencing; Thromboembolism; Thrombosis; Transcriptome; Tumor cells; Tumors; Venous Thromboembolism - blood; Venous Thromboembolism - diagnosis; Venous Thromboembolism - genetics
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.13926

Essentials The underlying pathophysiological mechanisms behind cancer‐associated thrombosis are unknown. We compared expression profiles in tumor cells from patients with and without thrombosis. Tumors from patients with thrombosis showed significant differential gene expression profiles. Patients with thrombosis had a proinflammatory status and increased fibrin levels in the tumor. Summary Background Venous thromboembolism (VTE) is a frequent complication in patients with cancer, and is associated with significant morbidity and mortality. However, the mechanisms behind cancer‐associated thrombosis are still incompletely understood. Objectives To identify novel genes that are associated with VTE in patients with colorectal cancer (CRC). Methods Twelve CRC patients with VTE were age‐matched and sex‐matched to 12 CRC patients without VTE. Tumor cells were isolated from surgical samples with laser capture microdissection approaches, and mRNA profiles were measured with next‐generation RNA sequencing. Results This approach led to the identification of new genes and pathways that might contribute to VTE in CRC patients. Application of ingenuity pathway analysis indicated significant links with inflammation, the methionine degradation pathway, and increased platelet function, which are all key processes in thrombus formation. Tumor samples of patients with VTE had a proinflammatory status and contained higher levels of fibrin and fibrin degradation products than samples of those without VTE. Conclusion This case–control study provides a proof‐of‐principle that tumor gene expression can discriminate between cancer patients with low and high risks of VTE. These findings may help to further unravel the pathogenesis of cancer‐related VTE. The identified genes could potentially be used as candidate biomarkers to select high‐risk CRC patients for thromboprophylaxis.