Tumor‐expressed microRNAs associated with venous thromboembolism in colorectal cancer

Abstract

Background Colorectal cancer patients have an increased risk of developing venous thromboembolism (VTE), resulting in increased morbidity and mortality. Because the exact mechanism is yet unknown, risk prediction is still challenging; therefore, new biomarkers are needed. MicroRNAs (miRNAs) are small, relatively stable RNAs, that regulate a variety of cellular processes, and are easily measured in body fluids. Objective The aim of this study was to identify novel tumor‐expressed miRNAs associated with VTE. Methods In a cohort of 418 colorectal cancer patients diagnosed between 2001 and 2015 at the Leiden University Medical Center, 23 patients (5.5%) developed VTE 1 year before or after cancer diagnosis. Based on availability of frozen tumor material, tumor cells of 17 patients with VTE and 18 patients without VTE were isolated using laser capture microdissection and subsequently analyzed on the Illumina sequencing platform NovaSeq600 using 150‐bp paired‐end sequencing. Cases and controls were matched on age, sex, tumor stage, and grade. Differential miRNA expression was analyzed using edgeR. Results A total of 547 miRNAs were detected. Applying a 1.5‐fold difference and false discovery rate of <0.1, 19 tumor‐miRNAs were differentially regulated in VTE cases versus controls, with hsa‐miR‐3652, hsa‐miR‐92b‐5p, and hsa‐miR‐10,394‐5p as most significantly downregulated. Seven of the 19 identified miRNAs were predicted to regulate the gonadotropin‐releasing hormone receptor pathway. Conclusion We identified 19 differentially regulated tumor‐expressed miRNAs in colorectal cancer‐associated VTE, which may provide insights into the biological mechanism and in the future might have potential to serve as novel, predictive biomarkers.

Advances in microRNA regulation of deep vein thrombosis through venous vascular endothelial cells (Review)

“…Oto et al (96) identified seven miRNAs, including miR-423-5p, as biological markers capable of predicting venous thrombosis in pancreatic ductal adenocarcinoma and distal extrahepatic cholangiocarcinoma. Similarly, four miRNAs, including miR-3652, were found to be significantly downregulated in patients with colorectal cancer with VTE, suggesting their potential as novel predictive biomarkers (97). Morelli et al (98) observed a positive correlation between plasma levels of miR-145 and the absence of VTE, proposing miR-145 as a potential target for VTE prevention (98).…”