Identification and evaluation of a reliable, non-invasive diagnostic method using serum microRNA expression to diagnose high-risk colorectal cancer candidates

e15519 Background: Screening is of paramount importance in early colorectal cancer detection which can significantly reduce its mortality. This study aims to identify a non-invasive diagnostic method using serum microRNA expression to diagnose colorectal cancer patients. Methods: Serum samples were prospectively collected from CRC patients or normal subjects during 2017 to 2021 in Queen Mary Hospital of Hong Kong and divided into 3 study cohorts: Training cohort (n = 129 per group), Validation cohort (n = 200 per group) and Prediction cohort (n = 260). Quantitative PCR was applied to detect the serum level of 20 candidate microRNAs. Multiple linear regression was used to formulate a serum microRNA panel for diagnosing CRC patients. The performance was evaluated by ROC analysis. The cost-effectiveness was investigating by comparing the cost of two CRC diagnostic strategies comprising of (i) colonoscopy alone and (ii) microRNA panel and followed by colonoscopy strategies to microRNA panel tested positive patients. Results: The values of 3 pairs of serum microRNAs, including miR-106b/miR-1246, miR-106b/miR-16 and miR-106b/miR-21 showed statistical significant difference between CRC patients and normal subjects. A serum microRNA panel formulated from these 3 pairs of microRNAs was able to diagnose CRC patients from normal subjects with high accuracy for both training cohort [AUC: 0.9078 (95% CI, 0.9122 To 0.9734; p < 0.0001)] and Validation cohort (AUC: 0.8904), suggesting that this microRNA panel had a consistent performance across different patient cohorts. Our prediction cohort showed that this microRNA panel was able to screen CRC patients with 85.8% sensitivity, 80.95% specificity, 86.9% positive predictive value and 79.4% negative predictive value. Cost-effectiveness analysis revealed that the strategy of combining serum miRNA test and colonoscopy was a more cost-effective approach compared to colonoscopy alone. The average cost saved per patient was around HK$4010. Conclusions: The serum miRNA test was a feasible, promising and cost-effective non-invasive biomarker for diagnosing CRC patients from normal subjects.