Table 4.
Exosomes as biomarkers for cancer liquid biopsy
| Cancer types | Exosome sources | Sample volume | Exosomal biomarker | Clinical samples | Diagnostic performance | Clinical significance | Ref. |
|---|---|---|---|---|---|---|---|
| Gastric Cancer | Serum | lnc HOTTIP | 126 GC patients; 120 healthy donors | AUC = 0.827 | Early diagnosis | [191] | |
| Serum | miR-15b-3p | 108 GC patients; 108 healthy donors | AUC of 0.820; specificity of 80.6%; sensitivity of 74.1% | Early diagnosis | [192] | ||
| HCC | Plasma | 100 μL | AFP; GPC3; ALB; APOH; FABP1; FGB; FGG; AHSG; RBP4; TF mRNA | 36 HCC patients; 26 Cirrhosis | AUC of 0.87; sensitivity of 93.8%; specificity of 74.5% | Early diagnosis | [61] |
| Serum | 500 μL | miRNA-21; lncRNA-A TB | 72 HCC patients | Higher in HCC patients | Prognostic significance | [189] | |
| Serum | miR-21 | Higher in HCC patients | Early diagnosis | [193] | |||
| Serum | 250 μL | miR-92b | 28 non-HCC; 28 HCC patients without recurrence; 43 HCC patients with early recurrenc | Sensitivity of 85.7%; specificity of 86.0%; AUC = 0.925 | Early recurrence diagnosis after LDLT | [194] | |
| Serum | 100 μL | CEA; GPC-3 and PD-L1 | 12 HCC patients; 12 hepatitis B; 6 healthy donors | Higher in HCC patients | Early diagnosis and progression monitoring | [112] | |
| PDAC | Plasma | 500 μL | miRNA-10b | 3 PDAC Patients; 3 CP Patients; 3 healthy donors | Higher in PDAC patients | Early diagnosis and progression monitoring | [173] |
| Plasma | miRNA-10b | PDAC patients; CP patients and healthy donors | Higher in PDAC patients | Early diagnosis | [195] | ||
| Mouse plasma samples | miR-3970-5p | 9 healthy donors; 9 PanIN patients; 9 PDAC patients | Accuracy of 65% | Early diagnosis | [196] | ||
| Serum | 250 μL | Glypican1 | 192 patients; 100 healthy donors | Sensitivity of 100%; specificity of 100%; positive predictive value of 100%; negative predictive value of 100%; AUC of 1.0 | Early diagnosis | [38] | |
| Plasma | 25 μL | Glypican1 | 20 PDAC patients; 7 benign pancreatic disease; 11 healthy donors | 99% sensitivity and 82% specificity | Stage classification | [197] | |
| Serum | 5 μL | EpCAM, Glypican1 | 90% accuracy for pancreatic cancer or normal pancreatic epithelial cell lines; 87 and 90% predictive accuracy for HC and EPC individual samples | Early diagnosis | [198] | ||
| Serum | 2 μL | MIF | 4 patients at stage 1 ~ 2; 37 patients at stage 3 | Discriminatory sensitivity of 95.7% | Stage classification | [199] | |
| CRC | Serum | hsa-circ-0004771 | 179 patients; 45 healthy donors | AUC of 0.86, 0.88 to differentiate stage I/II CRC patients and CRC patients from HCs | Early diagnosis | [200] | |
| Plasma | 25 μL | Epcam-CD63 | 59 cancer patients; 20 healthy donors | AUC of 0.96 | Early diagnosis; prognosis prediction | [125] | |
| NSCLC | Plasma | miRNA-21; miRNA-139; miRNA-200; miRNA-378 | 5 patients; 5 healthy donors | Higher in NSCLC patients | Early diagnosis | [123] | |
| Plasma | 1 mL | miRNA-21 | NSCLC patients; recurrence of NSCLC patients; healthy individuals | Higher in NSCLC patients | Early diagnosis and drug resistance in advanced cancers | [201] | |
| Plasma | 1.5 mL | CD63; EGFR; EpCAM | 4 patients; 4 treated patients; 4 healthy donors | Higher in NSCLC patients | Early diagnosis and therapeutic effect evaluation | [159] | |
| Serum | 50 μL | PD-L1 | 5 patients; 4 healthy donors | Higher in NSCLC patients | Early diagnosis | [132] | |
| Serum | 4 μL | PD-L1 | 7 patients at stage 1 ~ 2; 10 patients at stage 3 ~ 4; 12 healthy controls | AUC of 0.97 | Early diagnosis | [90] | |
| Breast Cancer | Plasma | EpCAM | 6 BC patients; 3 healthy donors | Higher in BC patients | Early diagnosis | [71] | |
| Plasma | EpCAM; HER2 | 10 BC patients; 5 healthy donors | AUC of 1; AUC of 1 | Early diagnosis | [134] | ||
| Serum | 3.6 μL | EpCAM | 20 BC patients; 10 healthy donors | AUC BC versus HD = 0.99; AUC HER2+ BC versus HER2– BC = 0.94 | Cancer classification | [202] | |
| Serum | PD-L1 | 7 patients with metastatic; 8 patients without metastatic; 6 healthy donors | Higher in BC patients | Prognosis prediction and progression monitoring | [114] | ||
| Blood | CA153 | 104 BC patients; 100 breast hyperplasia patients and 100 healthy controls | Higher in BC patients | Differential diagnosis | [203] | ||
| Serum | miR-21; miR-222; miR-200c | Luminal, HER2+, and TN breast cancer patients | Higher in BC patients | Classification of molecular subtypes of breast cancer | [204] | ||
| Plasma | 1 μL | CA153; EpCAM | 36 MBC patients before salvage treatment; 21 NMBC patients before surgical therapy; 66 age-matched healthy donors | AUPRC CA153 = 0.9286 | Differential diagnosis of BC and healthy donors | [69] | |
| AUPRC EpCAM = 0.9709 | |||||||
| Plasma | 1 μL | CA153; CA125; CEA; HER2; EGFR; PSMA; EpCAM; VEG | 36 MBC patients before salvage treatment; 21 NMBC patients before surgical therapy; 66 age-matched healthy donors | AUPRC of 0.9826 | Differential diagnosis of BC and healthy donors | [69] | |
| Plasma | 1 μL | CA153; CA125; CEA; HER2; EGFR; PSMA; EpCAM; VEG | 36 MBC patients before salvage treatment; 21 NMBC patients before surgical therapy; 66 age-matched healthy donors | AUPRC of 0.8672 | Differential diagnosis of MBC and NMBC | [69] | |
| Plasma samples | EpCAM | Various breast cancer patients and healthy individuals | Higher in BC patients | Early diagnosis | [115] | ||
| Prostate Cancer | Urine | 50-150 mL | miR-196a; miR-143-3p; miR-196-5p; miR-501-3p; | 28 PCA patients; 19 healthy donors | AUC miR-196a = 0.92 | Early diagnosis | [205] |
| AUC miR143-3p = 0.72 | |||||||
| AUC miR196-5p = 0.73 | |||||||
| AUC miR501-3p = 0.69 | |||||||
| Plasma | 750 μL | miR-217; miR-23b-3p | 10 patients; 10 healthy donors | Higher in PCA patients | Early diagnosis | [206] | |
| Serum | 400 μL | EphrinA2 | 50 PCA patients; 21 BPH patients; 20 healthy donors | AUC of 0.7666 | Early diagnosis; distinguish PCA from BPH patients | [207] | |
| Serum | 25 μL | EpCAM and PSMA | 10 PCA patients; 5 healthy donors | Higher in PCA patients | Early diagnosis | [127] | |
| Serum | TUBB3 mRNA | 52 mCRPC patients | Higher in PCA patients | Prognosis | [208] | ||
| Ovarian Cancer | Ascites | EpCAM; CD24 | 20 patients; 10 healthy donors | Higher in OVCA patients | Early diagnosis | [116] | |
| Plasma | 2 mL | CA125; EpCAM; CD24 | 15 patients; 5 healthy donors | AUC CA125 = 1.0 | Early diagnosis | [74] | |
| AUC EpCAM = 1.0 | |||||||
| AUC CD24 = 0.91 | |||||||
| Plasma | 20 μL | CD24; EpCAM; FRα | 20 OVCA patients; 10 non-cancer controls | AUC CD24 = 1.0 | Early diagnosis | [165] | |
| AUC EpCAM = 1.0 | |||||||
| AUC FRα = 0.995 | |||||||
| Plasma | 200 μL | miR-4732-5p | 21 healthy controls and 34 epithelial ovarian cancer patients | AUC miR-4732-5p = 0.889 | Early diagnosis | [209] |
ALB Albumin, APOH Apolipoprotein H, AUPRC Area under the Precision-Recall Curves, FABP1 Fatty acid binding protein 1, FGB Fibrinogen beta chain, FGG Fibrinogen gamma chain, AHSG Alpha 2-HS glycoprotein, RBP4 Retinol binding protein 4, TF Transferrin, LDLT Living donor liver transplantation, CP Chronic pancreatitis, PanIN Pancreatic intraepithelial neoplasia, PanIN Pancreatic intraepithelial neoplasia, MIF Migration inhibitory factor