Dynamic plasma microRNAs are biomarkers for prognosis and early detection of recurrence in colorectal cancer

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Abstract
Background: Plasma microRNAs (miRNAs) are promising non-invasive biomarkers for colorectal cancer (CRC) prognosis. However, the published studies to date have yielded conflicting and inconsistent results for specific plasma miRNAs. Methods: We have conducted a study using robust assays to assess a panel of nine miRNAs for CRC prognosis and early detection of recurrence. Plasma samples from 144 patients in a prospective CRC cohort study were collected at diagnosis, 6, 12, and 24 months after diagnosis. miRNAs were assayed by Taqman qRT–PCR to generate miRNA normalised copy numbers. Results: Preoperative high plasma miRNA levels were associated with increased recurrence risk for miR-200b (HR [95% CI]=2.04 [1.00, 4.16], P=0.05), miR-203 (HR=4.2 [1.48, 11.93], P=0.007), miR-29a (HR=2.61 [1.34,5.07], P=0.005), and miR-31 (HR=4.03 [1.76, 9.24], P=0.001). Both plasma miR-31 (AUC: 0.717) and miR-29a (AUC: 0.703) could discriminate recurrence from these patients without recurrence. In addition, high levels of miR-31 during surveillance was associated with a three-fold increased risk of recurrence across all time points. Dynamic postoperative plasma miR-141 and 16 levels correlated with recurrence in the surveillance samples. Conclusions: Pre-operative plasma miR-29a, 200b, 203, and 31 are potential CRC prognosis biomarkers. In addition, dynamic postoperative miR-31, 141 and 16 levels are potential biomarkers for the early detection of recurrence during CRC surveillance.

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