Table 6.
MicroRNA (MiRNA) as biomarker for lung cancer diagnosis.
| Study | Year | Assay | Tested miRNA | Study population | Sample | Diagnostic performance | |||
|---|---|---|---|---|---|---|---|---|---|
| Best predictors | S | E | AUC | ||||||
| Chen et al. (161) | 2008 | qRT-PCR and Solexa sequencing | 63 miRNAs | 75 healthy individuals 152 LC patients |
Serum | miR-25, miR-223 | – | – | – |
| Xie et al. (162) | 2009 | RT-PCR | miR-21 and miR-155 | 17 healthy individuals 23 NSCLC patients (13 ADC and 10 SCC) Staging: I: 3; II: 5; III: 7; IV: 8 |
Sputum | miR-21 | 70% | 100% | 0.902 |
| Yu et al. (163) | 2010 | RT-PCR | 7 miRNAs (miR-486, miR-126, miR-145, miR-21, miR-182, miR-375, and miR-200b) | Discovery set: 20 stage I ADC Case-control set: 36 healthy individuals 36 stage I ADC Validation set: 58 healthy individuals 64 NSCLC patients (33 ADC and 31 SCC) Validation set staging: I: 16; II: 15; III: 17; IV: 16 |
Sputum | miR-21, miR-486, miR-375, miR-200b | 70% | 80% | 0.839 |
| Shen et al. (164) | 2011 | RT-PCR | 12 miRNAs (miR-21, 126, 145, 139, 182, 200b, 205, 210, 375, 429, 486-5p, and 708) | 29 healthy individuals 58 NSCLC patients including 34 ADC and 24 SCC Staging: I: 15; II: 15; III: 12; IV: 16 |
Plasma | miRNA-21, -126, -210, and 486-5p | 86% | 97% | 0.926 |
| Shen et al. (165) | 2011 | RT-PCR | 5 miRNAs (miR-21, miR126, miR210, miR375, miR-486-5p) | - 80 benign SPNs patients - 76 malignant SPNs patients including 40 adenocarcinomas and 36 squamous cell carcinomas Staging: I: 24; II: 30; III–IV: 22 |
Plasma | miR-21, miR- 210, and miR-486-5p | 76% | 85% | 0.855 |
| Zheng et al. (166) | 2011 | RT-PCR | 15 miRNAs (miR-17, -21, -24, -106a, -125b, -128, -155, -182, -183, -197, -199b, -203, -205, -210 and -221) | 68 healthy individuals 74 LC patients: -17 SCLC -48 NSCLC (18 ADC, 23 SCC, 7 LCC and 9 others (carcinoid or mixed tumor) Staging: I: 21; II: 12; III: 11; IV: 30 |
Plasma | miR-155, miR-197, miR-182 | 81% | 87% | 0.901 |
| Boeri et al. (167) | 2011 | TaqMan Microfluidic cards | 15 miRNAs | 81 heavy smokers’ controls 53 LC patients (including 30 ADC) Staging: I: 28; II–III–IV: 25 |
Plasma | miR-17, miR-660, miR-92a, miR-106a, and miR-19b | 75% | 100% | 0.880 |
| Foss et al. (168) | 2011 | RT-PCR | 11 miRNAs (miR-1268, miR-574-5p, miR-1254, miR-1228, miR-297, miR-1225-5p, miR-923, miR-1275, miR-185, miR-483-5p, miR-320a) | Discovery set: 11 healthy individuals; 11 early-stage (I and II) NSCLC patients Validation set: 31 healthy individuals; 22 early-stage (I and II) NSCLC patients |
Serum | miR-1254 and miR-574-5p | 73% | 71% | 0.750 |
| Bianchi et al. (169) | 2011 | RT-PCR | 34 miRNAs | 30 healthy individuals 22 ADC 12 SCC Staging: I: 22; II–IV: 12 |
Serum | – | 71% | 90% | 0.890 |
| Heegaard et al. (170) | 2012 | RT-PCR | 30 miRNAs | 220 early-stage NSCLC patients 220 healthy individuals Staging: I: 180; II: 40 |
Serum | miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR27a, miR-106a, miR-29c | – | – | 0.602 |
| Sozzi et al. (171) | 2014 | RT-PCR | 24 miRNAs | 870 healthy individuals (690 smokers) 69 LC patients (55 smokers) Staging: I: 37; II–III: 12; IV: 19 |
Plasma | – | 87% | 81% | – |
| Shen et al. (172) | 2014 | RT-PCR | 12 miRNAs (miRs-21, 31, 126, 139, 182, 200b, 205, 210, 375, 429, 486, and 708) | Training set: 68 cancer-free smokers; 66 LC patients (27 ADC, 26 SCC and 13 SCLC) Training set staging of the NSCLC patients: I: 17; II: 18; III–IV: 18 Testing set: 73 cancer-free smokers; 64 LC patients (30 ADC, 28 SCC, 6 SCLC) Testing set staging of the NSCLC patients: I: 19; II: 19; III–IV: 20 |
Sputum | miR-31, miR-210 | 65% | 89% | 0.830 |
| Wang et al. (173) | 2014 | RT-PCR | 9 miRNAs(miR-20a, miR-25, miR-486-5p, miR-126, miR-125a-5p, miR-205, miR-200b, miR-21, and miR-155) | 111 healthy individuals 142 LC patients (including 101 ADC, 22 SCC and 10 SCLC) Staging: I: 70; II: 24; III: 21; IV: 27 |
Serum | miR-125a-5p, miR-25, and miR-126 | 88% | 83% | 0.930 |
| Montani et al. (174) | 2015 | RT-PCR | 34 miRNAs | 972 healthy individuals 36 LC patients (28 ADC and 5 SCC) Staging: I: 31; II–III: 5 |
Serum | miR-92a-3p, miR-30b-5p, miR-191-5p, miR-484, miR-328-3p, miR-30c-5p, miR-374a-5p, let-7d-5p, miR-331-3p, miR-29a-3p, miR-148a-3p, miR-223-3p, miR-140-5p | 75% | 78% | 0.850 |
| Xing et al. (175) | 2015 | RT-PCR | 13 miRNAs (miR205; miR708; miR375; miR200b; miR182; miR155; miR372; miR143; miR486-5p; miR126; miR31; miR21; miR210) | Training set: 62 benign SPNs; 60 malignant SPNs (with 27 ADC and 29 SCC) Training set staging: I: 39; II: 21 Internal Testing set: 69 benign SPNs; 67 malignant SPNs (including 30 ADC and 31 SCC) Internal Testing set staging: I: 45; II: 22 External Testing set: 79 benign SPNs; 76 malignant SPNs (including 34 ADC and 35 SCC) External Testing set staging: I: 51; II: 25 |
Sputum | miR-21, miR-31, miR-210 | 82–88% | 81–87% | 0.920 |
| Wang et al. (176) | 2015 | RT-PCR | 16 miRNAs (miR-193a-3p, miR-214, miR-7, miR-25, miR-483-5p, miR-523, miR-885-5p, miR-520c-3p, miR-484, miR-720, miR-133a, miR-337-5p, miR-150, miR-1274b, miR-342-3p, miR-145) | 48 healthy individuals 56 benign nodules 108 NSCLC patients (including 52 ADC and 27 SCC) Staging: I: 43; II: 15; III: 29; IV: 17 |
Serum | miR-483-5p, miR-193a-3p, miR-214, miR-25, and miR-7 | 95% | 84% | 0.952 |
| Kim et al. (177) | 2015 | RT-PCR | 5 miRNAs (miR-21, miR-143, miR-155, miR-210, and miR-372) | 10 cancer-free controls 21 early-stage NSCLC patients (13 ADC, 5 SCC and 3 LCC) Staging: I: 12; II: 9 |
BAL fluid/Sputum | miR-21, miR-143, miR-155, miR-210, and miR-372 | Patients BAL vs controls sputum: 86%Sputum: 68% | Patients BAL vs controls sputum: 100%Sputum: 90% | |
| Li et al. (178) | 2015 | RT-PCR | 10 miRNAs (miR-126, miR-150, miR-155, miR-205, miR-21, miR-210, miR-26b, miR-34a, miR-451 and miR-486) | 11 healthy individuals 11 early-stage NSCLC patients Staging: I–II: 11 |
Plasma | miR-486 and miR-150(individually) | miR-486: 91%miR-150: 82% | miR-486: 82%miR-150: 82% | miR-486: 0.926miR-150: 0.752 |
| Fan et al. (179) | 2016 | Fluorescence quantum dots liquid bead | 12 miRNAs (miR-15b-5p, miR-16-5p, miR-17b-5p, miR-19-3p, miR-20a-5p, miR-28- 3p, miR-92-3p, miR-106-5p, miR-146-3p, miR-506, miR-579, and miR-664 | 54 healthy individuals 70 NSCLC patients (56 ADC, 12 SCC and 2 LCC) Staging: I: 49; II–III: 21 |
Serum | miR-15b-5p, miR-16-5p, miR-20a-5p | 94$ | 94% | 0.930 |
| Razzak et al. (180) | 2016 | RT-PCR | 3 miRNAs (miR-21, miR-210, miR-372) | 10 healthy individuals 21 Early-stage NSCLC patients (including 13 ADC and 4 SCC) 22 Advanced-stage NSCLC patients (10 ADC and 5 SCC) Staging: I: 14; II: 7; III: 14; IV: 8 |
Sputum | miR-21, miR-210, miR-372 | 67% | 90% | 0.926 |
| Bagheri et al. (181) | 2017 | RT-PCR | 6 miRNAs (miR-223, miR-212, miR-192, miR-3074, SNORD33 and SNORD37) | 17 healthy individuals 17 NSCLC patients (11 ADC and 6 SCC) Staging: I: 2; II: 3; III: 5; IV: 7 |
Sputum | miR-223 | 82% | 95% | 0.900 |
| Leng et al. (182) | 2017 | RT-PCR | 54 miRNAs | 30 cancer-free smokers 34 NSCLC patients (21 AC and 13 SCC) Staging: I: 19; II: 9; III–IV: 15 |
Plasma | miRs-126, 145, 210, and 205-5p | 92% | 97% | 0.960 |
| Lu et al. (183) | 2018 | RT-PCR | 13 miRNAs (miR-101, miR-133a, miR-17,miR-190b,miR-19a, miR-19b, miR-205, miR-26b, miR-375, miR-451, miR-601, miR-760, miR-765) | 203 normal individuals 258 LC patients (133 ADC, 76 SCC and 49 SCLC) Staging: I: 78; II: 27; III: 40; IV: 64 |
Plasma | miR-17, miR-190b, miR-19a, miR-19b, miR-26b, and miR-375 | 80% | 80% | 0.868 |
| Abu-Duhier et al. (184) | 2018 | Magnetic bead technology and TaqMan assays | miRNA-21 | 80 healthy individuals 80 NSCLC patients (60 ADC and 20 SCC) Staging: I: 2; II: 7; III: 26; IV: 46 |
Plasma | – | 80% | 80% | 0.891 |
| Xi et al. (185) | 2018 | RT-PCR | 12 miRNAs (miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210) | 15 benign pulmonary nodules 42 NSCLC patients Staging: IA: 29; IB: 10; II: 3 |
Plasma | miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, -210 (individually) | >55% | >60% | >0.680 |
| Li et al. (186) | 2019 | RT-PCR | 4 miRNAs (miRs-126-3p, 145, 210-3p and 205-5p) | 245 cancer-free smokers 239 NSCLC cases (111 AC, 102 SCC and 26 LCC) Staging: I: 72; II: 76; III–IV: 91 |
Plasma | miRs-126-3p, 145, 210-3p and 205-5p | 90% | 95% | – |
| Liang et al. (187) | 2019 | RT-PCR | miRNA-30a-5p | 20 healthy individuals 38 lung benign lesions104 LC patients (including 75 ADC, 20 SCC and 5 SCLC) Staging: I–IIA: 62; IIB–IV: 42 |
Plasma | – | 80% | 61% | 0.820 |
| Xi et al. (188) | 2019 | RT-PCR | 10 miRNAs (miR-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miR-210) | 13 benign pulmonary nodules 39 NSCLC patients staging: 0–IA: 31; IB: 7; IIA: 1 |
Plasma | miRNA-146a, -200b, and -7 | 72% | 69% | 0.781 |
| Liao et al. (189) | 2020 | RT-PCR | 2 miRNAs in sputum (miRs‐31‐5p and 210‐3p)3 miRNAs in plasma (miRs‐21‐5p, 210‐3p, and 486‐5p) | 55 cancer-free smokers 56 NSCLC patients (31 ADC and 25 SCC) Staging: I: 18; II: 17; III–IV: 21 |
Plasma and Sputum | Sputum: miRs‐31‐5p and 210‐3pPlasma: miRs‐21‐5p | 84% | 91% | 0.930 |
ADC, adenocarcinoma; AUC, area under the curve; BAL, bronchoalveolar lavage; E, specificity; LC, lung cancer; NSCLC, non-small cell lung cancer; RT-PCR, real time polymerase chain reaction; S, sensitivity; SCC, squamous cell carcinoma; SCLC, small cell lung cancer; SPN, solitary pulmonary nodules.