Table 1. Studies aimed to identify diagnostic miRNA for CRC through high-throughput screening and subsequent qPCR validation.
| Study | Country | Sample type | Discovery phase (method and sample population) | Validation phase(s) (method and sample population) | Candidate miRNAs (expression) | AUC (95% CI) | SE | SP |
|---|---|---|---|---|---|---|---|---|
| Ghanbari et al. 2015 (48) | Iran | Plasma | miRNA Microarray system (Agilent); 37 CRC, 8 controls | qRT-PCR; 61 CRC, 24 controls | miR-142-3p (↓) | 0.71 | – | – |
| miR-26a-5p (↓) | 0.67 | – | – | |||||
| Giráldez et al. 2013 (49) | Spain | Plasma | SAM-Bead Array platform (Illumina); 21 CRC, 20 advanced adenoma, 20 controls | qRT-PCR; 42 CRC, 40 advanced adenomas, 53 controls | miR19a, miR19b (all ↑) | 0.82 (0.73–0.90) | 78.57% | 77.36% |
| miR19a, miR19b, miR15b (all ↑) | 0.84 (0.76–0.92) | 78.57% | 79.25% | |||||
| Hofsli et al. 2013 (50) | Norway | Serum | miRCURY LNA Universal RT microRNA PCR (Exiqon) (375 miRNAs); 30 CRC (stage IV), 10 controls | miRCURY LNA Universal RT microRNA PCR (34 miRNAs); 40 CRC (stage I,II), 10 controls | miR-423-5p, miR-210, miR-720, miR-320a and miR-378 (all ↑) | – | – | – |
| miR-106a, miR-143, miR-103, miR-199a-3p, miR-382 and miR-151-5p (all ↓) | – | – | – | |||||
| Imaoka et al. 2016 (51) | Japan | Serum | Microarray analysis; 3 CRC, 3 adenoma, 3 controls | qRT-PCR; 211 CRCs, 56 adenomas, 57 controls | miR-1290(↑) | CRC vs. controls 0.83 | 7.01% | 91.2% |
| Adenoma vs. controls 0.72 | 46.4% | 91.2% | ||||||
| Kanaan et al. 2013 (52) | Kentucky (USA) | Plasma | TaqMan low-density array card (life technologies) 380 miRNAs; 20 CRC, 9 adenoma, 12 controls | qRT-PCR; 45 CRC, 16 adenoma, 26 controls | miR-139-3p, miR-431 (all ↑) | CRC vs. controls; 0.83 (0.73–0.93) | 91% | 57% |
| Li et al. 2015 (53) | China | Serum | TaqMan low-density array (applied biosystems) (749 miRNAs); pooled 20 CRC, 20 controls | qRT-PCR; 175 stage II/III CRC patients, 130 controls | miR-145(↓) | 0.87 (0.84–0.91) | – | – |
| miR-17-3p(↑) | 0.78 (0.73–0.83) | – | – | |||||
| miR-106a(↑) | 0.81 (0.77–0.86) | – | – | |||||
| miR-145(↓),miR-17-3p(↑), miR106a (↑) | 0.89 (0.85–0.92) | 78.5% | 82.8% | |||||
| Luo et al. 2013 (54) | Germany | Plasma | TaqMan microRNA array (applied biosystems) 667 miRNAs; 5 pools of CRC patients (N=50), 5 pools of controls (N=50) | qRT-PCR; 80 CRC, 50 advanced adenoma, 194 controls | miR-18a, miR-20a,miR21, miR-29a,miR-92a, miR-106b, miR-133a, miR-143,miR-145 (all ↑) | CRC vs. controls; 0.745 (0.708–0.846) | – | – |
| Ng et al. 2009 (55) | China | Plasma | Cancer microRNA array (system biosciences) 95 miRNAs; 5 CRC, 5 controls | qRT-PCR; (I) 25 CRC,20 controls; (II) 90 CRC 50 controls | miR-17-3p (↑) | (II) 0.717 (0.633–0.800) | (II) 64% | 70% |
| miR-92 (↑) | (II) 0.885 (0.828–0.942) | (II) 89% | 70% | |||||
| Sun et al. 2016 (56) | China | Plasma | TaqMan array (life technologies) (754 miRNAs); 40 CRC, 10 controls | qRT-PCR; 187 CRC, 47 controls | miR-96 (↑) | 0.740 (0.650–0.831) | 65.4% | 73.3% |
| Vychytilova-Faltejskova et al. 2016 (57) | Czech Republic | Serum | Illumina small RNA sequencing; pooled 144 CRC, 96 controls | qRT-PCR; 203 CRC, 100 controls | miR-23a-3p (↑) | 0.89 | – | – |
| miR-27a-3p (↑) | 0.70 | – | – | |||||
| miR-142 5p (↑) | 0.81 | – | – | |||||
| miR-376c-3p (↑) | 0.65 | – | – | |||||
| miR-23a-3p, miR-27a-3p, miR-142-5p, miR-376c-3p (all ↑) | 0.92 | 89% | 81% | |||||
| Wang et al. 2012 (58) | China | Plasma | miRCURY LNATM universal RT microRNA PCR system (exiqon, demark) (742 miRNAs); 10 CRC, 10 controls | qRT-PCR; 90 CRC, 43 advanced adenoma, 58 controls | miR-601 (↓) | CRC vs. controls; 0.747 (0.666–0.828) | 69.2% | 72.4% |
| miR-760 (↓) | CRC vs. controls; 0.788 (0.714–0.862) | 80% | 72.4% | |||||
| Wang et al. 2015 (59) | China | Plasma | Human microRNA microarrays Agilent technologies (723 miRNAs); 47 CRC, 33 controls | qRT-PCR; (I) 55 CRC, 57 controls; (II) 22 CRC, 27 controls | miR-409-3p (↑), miR-7 (↓), miR-93 (↓) | (I) 0.866 (0.788–0.923); (II) 0.897 | (I) 91%; (II) 82% | (I) 88%; (II) 89% |
| Xu et al. 2014 (60) | China | Plasma | TaqMan low density miRNA arrays [applied biosystems (754 miRNAs)]; 6 CRC, 6 controls | qRT-PCR; 88 CRC, 40 controls | miR-375 (↓) | 0.749 (0.654-0.844) | 76.92% | 64.63% |
| miR-206 (↑) | 0.705 (0.612-0.798 | – | – | |||||
| miR-375 (↓) miR-206 (↑) | 0.846 (0.775-0.917) | – | – | |||||
| Zheng et al. 2014 (61) | China | Serum | Miseq sequencing; pooled serum samples (30 CRC, 25 adenoma, 30 controls) | qRT-PCR; (I) 160 CRC, 66 CA patients, 94 controls; (II) 117 CRC, 73 adenoma, 102 controls | miR-19a-3p (↑) | (I) 0.849 | – | – |
| miR-92a-3p (↑) | (I) 0.890 | – | – | |||||
| miR-223-3p (↑) | (I) 0.871 | – | – | |||||
| miR-422a (↓) | (I) 0.843 | – | – | |||||
| miR-19a-3p, miR-223-3p, miR-92a-3p and miR-422a | (II) 0.951 (0.907–0.978 | – | – | |||||
| Zhu et al. 2017 (62) | China | Serum | Exiqon miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1 (168 miRNAs); 30 CRC, 30 controls | qRT-PCR; (I)136 CRC vs. 90 controls; (II) 30 CRC vs. 18 controls | miR-19a-3p, miR-21-5p, miR-425-5p (all ↑) | 0.830 (0.708–0.952) | – | – |
(↑), miRNAs upregulated in CRC patients compared to healthy subjects; (↓), miRNAs downregulated in CRC patients compared to healthy subjects. CRC, colorectal cancer; AUC, area under curve; SE, sensitivity; SP, specificity.