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

Zixu Yuan, Kelsey Baker, Mary W Redman, Lei Wang, Scott V Adams, Ming Yu, Brandon Dickinson, Karen Makar, Neli Ulrich, Jürgen Böhm, Michelle Wurscher, Maria Westerhoff, Steve Medwell, Ravi Moonka, Mika Sinanan, Alessandro Fichera, Kathy Vickers, William M Grady, Zixu Yuan, Kelsey Baker, Mary W Redman, Lei Wang, Scott V Adams, Ming Yu, Brandon Dickinson, Karen Makar, Neli Ulrich, Jürgen Böhm, Michelle Wurscher, Maria Westerhoff, Steve Medwell, Ravi Moonka, Mika Sinanan, Alessandro Fichera, Kathy Vickers, William M Grady

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.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of study population.
Figure 2
Figure 2
The 3-year recurrence-free survival (RFS) analyses for pre-operative plasma miRNAs. Kaplan–Meier analysis was made in CRC patients (N=122). (A–D) Higher pre-operative plasma miR-29a (P<0.01), miR-203 (P<0.01), miR-31 (P<0.01) and miR-200b (P=0.05) predict a shorter RFS. For each miRNA, the median value was used to divide the samples into those with high or low levels. The number of patients at risk is shown below each curve.
Figure 3
Figure 3
Preoperative plasma miR31 and 29a can discriminate patients developing recurrence. Analyses of receive operating characteristic (ROC) curve showed prognostic power of plasma miR31 (AUC: 0.717 (95% CI: 0.439, 0.995)) and miR29a (AUC: 0.703 (95% CI: 0.562, 0.845)), which could discriminate patients with recurrence from these without recurrence.
Figure 4
Figure 4
Dynamic changes of plasma miR141,16 at different time points in patients with or without recurrence. Plasma miR141 was decreased 24 months after surgery, comparing to baseline (P=0.035, paired t-test, n=9 pairs) and 12 months after surgery (P=0.014, paired t-test, n=9 pairs) in patients without recurrence (A and B). Plasma miR-16 increased 12 months after surgery comparing to baseline (P=0.036, paired t-test, n=10 pairs) in recurrence group (C and D). recur=recurrence. *P<0.05.

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Source: PubMed

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