Table 2.
Studies on clinical utility of exosomal proteins as biomarkers in lung cancer.
| Molecule | Sample | Number of Subjects | Isolation Methods | Characterization Methods | Utility | Comments | Authors |
|---|---|---|---|---|---|---|---|
| CD151, CD171, and tetraspanin 8 | Plasma | 336 LC + 126 C | EV array | - | Diagnosis | AUC calculated between LC and controls and when subdividing in AC, SCC and SCLC. NYESO1, HER2, EGFRvIII, SFTPD, Florilin1, CD142 and Mucin 16 also analyzed | Sandfeld-Paulsen et al. [111] |
| CD91 (+CEA) | Serum | Screening set: 10 C, 10 IP, 14 AC, 12 SCC Validation set: 54 C, 19 IP, 105 AC, 34 SCC |
Immune-affinity for screening set ELISA with anti-CD9 in validation set |
- | Diagnosis | Screening set: isolation by immune-affinity with anti-CD9 tips and proteomic study to identify CD9 Validation Set: ELISA with anti CD9 as capture antibody and anti-CD91 as detection antibody |
Ueda et al. [112] |
| AHSG and ECM1 | Serum | 125 NSCLC + 46 C | Ultracentrifugation | TEM/NTA/WB | Diagnosis (including early stage) | Differentially expressed proteins identified by mass spectrometry | Niu et al. [113] |
| Panel of 30 proteins | Plasma | 109 advanced NSCLC + 110 C | EV Array | - | Diagnosis | Array for 37 proteins | Jakobsen et al. [84] |
| SRGN, TPM3, THBS1 and HUWE1 | Plasma | 13 AC + 15 C | Density gradient | TEM/NTA/WB | Diagnosis | 108 differentially expressed proteins identified by mass spectrometry | Vykoukal et al. [114] |
| CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3 | Serum | 20 AC + 20 SCC + 20 SCLC + 20 C | Polyethylene glycol -based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM | TEM/NTA/DLS/WB | Diagnosis | Differentially expressed proteins identified by mass spectrometry; 55 confirmed by Western blot. CD5L highest AUC | Choi et al. [74] |
| LRG1 | Urine | 8 NSCLC + 10 C | Ultracentrifugation | TEM | Diagnosis | Differentially expressed proteins identified by mass spectrometry | Li et al. [115] |
| CD171 (1), NY-ESO-1 (2) | EDTA Plasma | 276 NSCLC | EV array | - | Prognosis: (1) OS, (2) HR | Array for 49 proteins | Sandfeld-Paulsen et al. [116] |
| PD-L1 | Plasma | 33 NSCLC | Precipitation | TEM/NTA/WB | Prognosis: OS and PFS | Quantification with Simoa Bead Technology | Yang et al. [117] |
| HSP70 | EDTA Plasma | 20NSCLC+ 14 C + 10 BC | Ultracentrifugation | NTA/TEM | Diagnosis, prognosis (metastasis detection), monitoring | HSP70 barely detected in plasma. Exosomal HSP70 correlates with tissue analysis | Chanteloup et al. [118] |
Abbreviations: AC: adenocarcinoma; AUC: area under ROC curve; BC: breast cancer; C: controls; CEA: carcinoembryonic antigen; CYFRA21-1: cytokeratin 19 fragment; DLS: dynamic light scattering; EDTA: ethylenediaminetetraacetic acid; EV: extracellular vesicles; HR: hazard ratio; IP: interstitial pneumonia; LC: lung cancer; NSCLC: non-small cell lung cancer; NTA: nanoparticle tracking analysis; OS: overall survival; P: pneumonia; PFS: progression-free survival; SCC: squamous carcinoma; SCLC: small cell lung cancer; T: tuberculosis; TEM: transmission electron microscopy; TNM: tumor-node-metastasis; WB: Western blot.