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. 2013 May 14;8(5):e62880.
doi: 10.1371/journal.pone.0062880. Print 2013.

Identification and evaluation of plasma microRNAs for early detection of colorectal cancer

Xiaoya Luo  1 , Christian Stock, Barbara Burwinkel, Hermann Brenner
Affiliations

Identification and evaluation of plasma microRNAs for early detection of colorectal cancer

Xiaoya Luo et al. PLoS One. .

Abstract

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers. Circulating microRNAs (miRNAs) have been suggested as potentially promising markers for early detection of CRC. We aimed to identify and evaluate a panel of miRNAs that might be suitable for CRC early detection.

Methods: MiRNAs were profiled by TaqMan MicroRNA Array and screened for differential expression in 5 pools of plasma samples of CRC patients (N = 50) and 5 pools of neoplasm-free controls (N = 50). Additional miRNAs were selected from a literature review. Identified candidates were evaluated in independent validation samples with respect to discrimination of CRC patients (N = 80) or advanced adenoma patients (N = 50) and neoplasm-free controls (N = 194). Diagnostic performance of the panel of miRNAs was assessed by multiple logistic regression, using bootstrap analysis to correct for over-optimism.

Results: Five miRNAs identified to be differentially expressed from TaqMan MicroRNA Array (miR-29a, -106b, -133a, -342-3p, -532-3p), and seven miRNAs reported to be differentially expressed in the literature (miR-18a, -20a, -21, -92a, -143, -145, -181b) were selected for validation. Nine of the twelve miRNAs (miR-18a, -20a, -21, -29a, -92a, -106b, -133a, -143, -145) were found to be differentially expressed in CRC patients and controls in the validation samples. The optimism-corrected area under the curve was 0.745 (95% confidence interval: 0.708-0.846). None of the selected miRNAs showed significant differential expression between advanced adenoma patients and neoplasm-free controls.

Conclusion: The identified panel of miRNAs could be of potential use in the development of a multi-marker blood based test for early detection of CRC.

Impact: The study underscores the high potential of plasma miRNAs for the improvement of current offers of non-invasive CRC screening.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Expression levels of microRNAs in 80 colorectal cancer patients and 144 neoplasm-free controls (normalized to miR-16, log2 scale at y-axis).
Box plots with smallest observation, lower quartile, median, upper quartile and largest observation are shown. The whiskers extend to the observations which are no more than 1.5 times the length of the box (interquartile range) away from the box. More extreme observations are considered outliers. P values are based on Wilcoxon tests.
Figure 2
Figure 2. Receiver operating characteristic curves using the panel of 12 selected microRNAs for discrimination of 80 colorectal cancer patients and 144 neoplasm-free controls.
Adjustment for over-optimism was done by the.632+ bootstrap method. Abbreviations: AUC, area under receiver operating characteristic curve.
See this image and copyright information in PMC

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Grants and funding

The authors have no support or funding to report.