Blood-based microRNAs as biomarkers for the diagnosis of colorectal cancer: a systematic review and meta-analysis

Abstract

Background: Colorectal cancer (CRC) is common and associated with significant mortality. Current screening methods for CRC lack patient compliance. microRNAs (miRNAs), identified in body fluids, are negative regulators of gene expression and are dysregulated in many cancers, including CRC. This paper summarises studies identifying blood-based miRNAs dysregulated in CRC compared with healthy controls in an attempt to evaluate their use as a screening tool for the diagnosis of CRC.

Methods: A search of electronic databases (PubMed and EMBASE) and grey literature was performed between January 2002 and April 2016. Studies reporting plasma or serum miRNAs in the diagnosis of CRC compared with healthy controls were selected. Patient demographics, type of patient sample (serum or plasma), method of miRNA detection, type of normalisation, and the number of significantly dysregulated miRNAs identified were recorded. Statistical evaluation of dysregulated miRNAs using sensitivity, specificity, and area under the curve (AUC) was performed.

Results: Thirty-four studies investigating plasma or serum miRNAs in the diagnosis of CRC were included. A total of 31 miRNAs were found to be either upregulated (n=17) or downregulated (n=14) in CRC cases as compared with controls. Fourteen studies identified panels of ⩾2 dysregulated miRNAs. The highest AUC, 0.943, was identified using a panel of 4 miRNAs with 83.3% sensitivity and 93.1% specificity. Meta-analysis of studies identifying a single dysregulated miRNA in CRC cases compared with controls was performed. Overall sensitivity and specificity of 28 individual miRNAs in the diagnosis of CRC were 76% (95% CI 72%-80%) and 76% (95% CI 72%-80%), respectively, indicating good discriminative ability of miRNAs as biomarkers for CRC. These data did not change with sensitivity analyses.

Conclusions: Blood-based miRNAs distinguish patients with CRC from healthy controls with high sensitivity and specificity comparable to other common and invasive currently used screening methods for CRC. In future, miRNAs may be used as a relatively non-invasive blood-based marker for detection of CRC.

Figure 1

Flow diagram of the literature search process and study inclusion.

Figure 2

QUADAS-2 assessment. Investigators' assessment regarding each domain for included studies. Risk of bias and applicability concerns' (A) graph and (B) summary.

Figure 3

Forest plots for studies on individual miRNA assays used in the diagnosis of CRC among the 19 studies included in the meta-analysis. (A) Estimates of sensitivity. (B) Estimates of specificity. A full color version of this figure is available at the British Journal of Cancer journal online.

Figure 4

Analysis performed for low-risk/low-concern studies with respect to QUADAS-2 quality assessment. (A) Quality sensitivity analysis. Overall sensitivity was 77% (95% CI 72–83%). (B) Quality specificity analysis. Overall specificity was 77% (95% CI 72–81%). A full color version of this figure is available at the British Journal of Cancer journal online.