Abstract Number: PB1103
Meeting: ISTH 2021 Congress
Background: Colorectal cancer (CRC) patients have an increased risk of developing venous thromboembolism (VTE), resulting in increased morbidity and mortality. Available risk prediction tools for identifying patients at high risk of VTE show poor clinical performance. MicroRNAs (miRNAs) are small RNAs, which regulate a variety of cellular processes, are relatively stable and are detectable in body fluids. We hypothesize that miRNAs can be used to improve VTE prediction in CRC patients.
Aims: The aim of this study is to identify novel tumor-expressed miRNAs associated with VTE.
Methods: In a cohort of 418 CRC patients diagnosed between 2001-2015 at the Leiden University Medical Center (LUMC), 23 patients developed VTE 1 year before or after cancer diagnosis. Based on availability of frozen tumor material, age, gender and tumor stage, 17 patients with VTE and 18 patients without VTE were selected. Tumor cells were isolated using laser capture microdissection and samples were subsequently analyzed on the Illumina sequencing platform NovaSeq600 using a 150 bp paired-end sequencing. The paired-end raw reads were processed using the BioWDL small-RNA pipeline version 1.2.0 developed at LUMC. Differential miRNA expression was analysed using edgeR; the Benjamini-Hochberg method was used to adjust p-values for false discovery.
A total of 548 miRNAs were detected. Applying a minimum 1.5 fold change (FC) difference and a FDR value of < 0.1, 14 miRNAs were differentially regulated in CRC patients with VTE, compared to without VTE (table 1 & figure 1). In a sub-analysis, we assessed miRNAs associated with VTE in the early disease course and not affected by cancer treatment (1 year before cancer diagnosis). Seven significant miRNAs were identified (downregulated; hsa-miR-10394-3p, hsa-miR-10394-5p, hsa-miR-483-5p, hsa-miR-182-5p, hsa-miR-3654; upregulated; hsa-miR-223-3p, hsa-miR-363-3p).
Conclusions: We identified 19 tumor-expressed miRNAs significantly expressed in cancer-associated VTE, which may have the potential to serve as novel, non-invasive predictive biomarkers for VTE in CRC.
To cite this abstract in AMA style:Anijs RJS, Laghmani EH, Ünlü B, Kielbasa SM, Mei H, Cannegieter SC, Klok FA, Kuppen PJK, Versteeg HH, Buijs JT. Identification of Tumor-expressed MicroRNAs Associated with Venous Thrombosis in Colorectal Cancer [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/identification-of-tumor-expressed-micrornas-associated-with-venous-thrombosis-in-colorectal-cancer/. Accessed September 16, 2021.
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