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.

The role of the miR‐200 family in epithelial–mesenchymal transition in colorectal cancer: a systematic review

“…miRs are transcribed in the nucleus as large RNA precursors called primary microRNAs. 9 31. 6,7 While microRNAs have several normal functions related to cell growth, development and differentiation, aberrant expression of these microRNAs may contribute to tumorigenesis.…”

“…8 Furthermore, altered expression of microRNAs in tumor tissue or serum may have a role in the diagnosis of patients with CRC. 9 31. In addition to being grouped into positional clusters, the miR-200 family can be organized into two functional groups, based on their seed sequences; miR-200b-200-c-429 and miR-200a-141.…”

Plasma miRNA can detect colorectal cancer, but how early?

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Recent years have attributed major knowledge in the research area of microRNA (miRNA), a group of short 20-22 bp nucleotides, noncoding RNAs which play key roles in many biological processes, including cancer development [6], and miRNAs have been shown to be remarkably stable in both tissue samples as well as in plasma and serum [7,8]. One reason for that is that miRNAs interact with Argonaute2, which keeps it protected from nuclease activity, therefore, making them excellent markers for blood-based detection of CRC [9][10][11].A number of studies have indeed shown that several miRNAs are of interest when aiming to detect CRC [12][13][14][15]. Kanaan et al [16] found a panel of eight circulating miRNAs (miR-532-3p, 331, -195, -17, -142-3p, -15b, -532, and -652) that could distinguish CRC from controls (AUC 0.829), Wang et al [17] identified miR-409-3p, -7, and -93 as panel that discriminated CRC from healthy persons (AUC 0.897), Wang et al [18] showed that miR-601 and

AbstractColorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early.

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“…A number of studies have indeed shown that several miRNAs are of interest when aiming to detect CRC [12][13][14][15]. Kanaan et al [16] found a panel of eight circulating miRNAs (miR-532-3p, 331, -195, -17, -142-3p, -15b, -532, and -652) that could distinguish CRC from controls (AUC 0.829), Wang et al [17] identified miR-409-3p, -7, and -93 as panel that discriminated CRC from healthy persons (AUC 0.897), Wang et al [18] showed that miR-601 and…”

Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics

“…Today, biomarker research has been transformed by the fields of genomics, proteomics, metabolomics, and lipidomics. As a result, the possible molecular nature of a biomarker today is as varied as there are substances in the body, and includes circulating tumoral DNA (e.g., mutated EGFR gene [ 7 ] ), the various types of RNA (particularly microRNA [ 8 ] ), peptides and proteins (e.g., hormones, receptors, antibodies), [ 9 ] lipids and other metabolites, [ 10 ] circulating tumor cells, and non‐cellular vesicles called “exosomes”. [ 11 ] There are currently great expectations (e.g., [ 12–15 ] ) that these molecular and cellular biomarkers will provide the needed specificity, sensitivity, reproducibility, and cost‐effectiveness for the early diagnosis of particular types of cancer.…”