Table 3.
BALF-derived EVs for lung cancer
| Study population | Type | Methods of isolation | Cargos | Targets | Sn/Sp (%) | Comparison (Sn/Sp) (%) | Comments | Ref. |
|---|---|---|---|---|---|---|---|---|
| NSCLC (n = 23): EGFR mutation 14 vs. WT 9 | EVs | Differential centrifugation† 1. 1000 g × 15 min 2. 200,000 g × 1 h |
DNA |
EGFR mutation |
100/ 100 |
BALF cfDNA: 71.4/100. Plasma EV DNA: 55.0/NA (unpaired) Plasma cfDNA: 30.0/NA (unpaired) |
1. Liquid biopsy with EVs DNA was more sensitive compared to using cfDNA. 2. Sensitivities of BALF samples were significantly higher compared to plasma samples for both cfDNA and EVs DNA. | 94 |
| Patients resistant to EGFR-TKIs (n = 9) |
T790M mutation | 55.5/NA | BALF cfDNA: 33.3/NA Re-biopsy tissue: 22.2/NA (paired) |
BALF-EVs DNA had higher efficiency for detecting T790M mutation compared to tissue re-biopsy. | ||||
| Lung cancer (n = 137): EGFR mutation 54 vs. WT 83 | EVs | Differential centrifugation 1. 1000 g × 10 min 2. 200,000 g × 1 h |
DNA | EGFR mutation | 75.9/86.7 |
T1: 40/NA; T4: 100/NA N0: 63.3/NA; N3: 100/NA M0: 43.5/NA; M1: 100/NA |
BALF EVs-based EGFR genotyping had increased sensitivity with escalating TMN stage and even more useful when biopsy was not feasible. | 95 |
| NSCLC III-IV (n = 224): EGFR mutation 93 vs. WT 131 | EVs | Differential centrifugation 1. 1000 g × 10 min 2. 200,000 g × 1 h |
DNA | EGFR mutation | 97.8/96.9 | Plasma cfDNA: 48.5/86.3 (unpaired) |
BALF-derived EVs testing in advanced NSCLC was rapid with high accuracy, serving as an alternative for tissue biopsy for guiding prompt EGFR-TKI treatment. | 96 |
| NSCLC (n = 30) and non-tumor patients (n = 75) | Exosomes | Differential centrifugation 1. 500 g × 10 min 2. 17,000 g × 20 min 3. 120,000 g × 90 min |
miRNA | miRNA profiles | NA | NA | 1. Exosome levels were significantly higher in plasma than in BALF samples in patients with and without cancer. 2. The concentrations of plasma miRNAs was higher in tumor patients when comparing non-tumors but were similar for BALF miRNA. |
97 |
| Lung adenocarcinoma (n = 13) and benign lung diseases (n = 15) | Exosomes | Commercial kit (ExoQuick Exosome Precipitation Solution) | miRNA | miR-126/ Let-7a |
NA | NA | Exosomal miRNA-126 and Let-7a levels were higher in the BALF of adenocarcinoma than benign BALF. | 98 |
| NSCLC patients with EGFR 19del mutation (n = 10) | Exosomes | Differential centrifugation 1. 300 g×10 min 2. 16,500 g × 20 min 3. 120,000 g × 70 min |
mRNA | MET | NA | NA | MET was detected in plasma- and BALF‡-derived exosomes in metastasis without a significant difference between the two body fluids. |
99 |
| NSCLC (n = 22) and healthy volunteers (n = 12) | EVs | Differential centrifugation 1. 500 g × 10 min 2. 2,500 g × 12 min 3. 17,000 g × 160 min |
Protein | SOCS3 | NA | NA | The protein level of SOCS3 in the BALF was significantly reduced, independent of histopathologic type and smoking status. | 100 |
| Lung cancer (n = 12) and non-lung cancer (n = 12) | EVs | Differential centrifugation 1. 3000 g × 20 min 2. 12,000 g × 1 h 3. 100,000 g × 2 h |
Proteome | DNMT3B | NA | NA | 1. Proteome complexity of BALF-EVs correlated with lung cancer stage IV and mortality within 2 years of follow-up. 2. DNMT3B complex was significantly up-regulated in tumor tissue and BALF-EVs. |
101 |
Sn, sensitivity; Sp, specificity; NSCLC, non-small-cell lung cancer; WT, wild type; EVs, extracellular vesicles; NA, not available; TKIs, tyrosine kinase inhibitors.
†Indicates a separation technique separating and removing components other than EVs from BALF in a stepwise manner, and all the centrifugation steps are performed at 4°C.
‡Plasma and BALF were collected at the time of primary diagnosis and after the treatment with icotinib/gefitnib within a follow-up period of 3–6 months.