Dataset Information

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.

SUBMITTER: Anijs RJS

PROVIDER: S-EPMC9248312 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundVenous thromboembolism (VTE) is the most common preventable cause of 30-day post-operative mortality, with many events occurring after hospital discharge. High-level evidence supports post-discharge VTE chemoprophylaxis following abdominal/pelvic cancer resection; however, some studies support a more tailored approach. Our objectives were to (1) identify risk factors associated with post-discharge VTE in a large cohort of patients undergoing colorectal cancer resection and (2) develop a post-discharge VTE risk calculator.MethodsPatients who underwent colorectal cancer resection from 2012 to 2016 were identified from ACS NSQIP colectomy and proctectomy procedure-targeted modules. Multivariable logistic regression was used to identify factors associated with post-discharge VTE. Incorporating pre-operative, intra-operative, and post-operative variables, a post-discharge VTE risk calculator was constructed and validated.ResultsOf 51,139 patients, 387 (0.76%) developed post-discharge VTE. Pre-operative factors associated with post-discharge VTE included BMI (e.g., morbidly obese OR 2.27, 95% CI 1.65-3.12 vs. normal BMI), and thrombocytosis (OR 1.41, 95% CI 1.03-1.92). Intra-operative factors included operative time (4-6 h OR 1.56, 95% CI 1.12-2.17; > 6 h, OR 1.85, 95% CI 1.21-2.84, vs. < 2 h), and type of operation (e.g., open partial colectomy OR 1.67, 95% CI 1.30-2.16 vs. laparoscopic partial colectomy). Post-operative factors included anastomotic leak (OR 2.05, 95% CI 1.31-3.21) and post-operative ileus (OR 1.39, 95% CI 1.07-1.79). Using the risk calculator, the predicted probability of post-discharge VTE ranged from 0.04 to 10.29%. On a 10-fold cross validation, the calculator's mean C-Statistic was 0.65.ConclusionsPatient-specific factors are associated with varying rates of post-discharge VTE. We present the first post-discharge VTE risk calculator designed for use at the time of discharge following colorectal cancer resection.