Table 1 sEV RNA biomarkers for PDAC diagnosis/prognosis
RNA types | Biomarkers | Sources | Patient numbers | Discoveries and diagnostic performance | Ref. | |
|---|---|---|---|---|---|---|
miRNA | miR-196a | Plasma | Stage I-IIA n = 15 | Higher miR-196a expression in sEVs from PDAC patients with AUC of 0.81 | [58] | |
|  | miR-10b | Plasma | N = 3 | The expression of miR-10b was significantly higher in sEVs from PDAC patients when compared with patients with chronic pancreatitis (CP) or normal controls | [59] | |
|  | miR-451a | Plasma | Stage I n = 7, stage II n = 43 | The level of miR-451a showed a significant association with cancer diagnosis and cancer stage discrimination (stage I vs. healthy volunteers P= 0.019, stage II vs. healthy volunteers P< 0.001, stage II vs. stage I P= 0.041) | [60] | |
|  | miR-125b-3p, miR-122-5p, and miR-205-5p | Plasma | N = 65 | MiR-125b-3p, miR-122-5p, and miR-205-5p were overexpressed in PDAC patients than healthy people with AUC values of 0.782, 0.814, and 0.857, respectively | [61] | |
|  | miR-10b, miR-21, miR-30c, miR-181a and miR-let7a | Plasma | N = 29 | High levels of miR-10b, miR-21, miR-30c, and miR-181a and a low level of miR-let7a in sEVs could differentiate PDAC from normal control and CP samples with AUC of 1.00 | [13] | |
|  | miR-1226-3p | Serum | N = 17 | The expression of miR-1226-3p was downregulated in PDAC patients compared to benign pancreatic lesions with AUC of 0.74 | [62] | |
|  | miR-17-5p and miR-21 | Serum | N = 22 | High expression of miR-17-5p and miR-21 in sEVs from PDAC patients with AUC of 0.887 and 0.897, respectively | [63] | |
|  | miR-451 and miR-720 | Serum | N = 52 | PDAC patients had significantly higher levels of miR-451 and lower levels of miR-720 in sEVs than healthy controls with AUC of 0.93 and 1.00, respectively | [64] | |
|  | miR-191, miR-21 and miR-451a | Serum | N = 32 | The expression of miR-191, miR-21 and miR-451a in sEVs was significantly up-regulated in patients with pancreatic cancer and IPMN compared to controls with AUC of 0.788, 0.826 and 0.759, respectively | [65] | |
|  | miR-1246, miR-4644, miR-3976 and miR-4306 | Serum | N = 131 | The level of miR-1246, miR-4644, miR-3976 and miR-4306 were significantly upregulated in 83% of the cancer patient group, but rarely in control groups, these marker panels remarkably improved the sensitivity (1.00, CI: 0.95-1) with a specificity of 0.80 (CI: 0.67–0.90) | [66] | |
|  | miR-1246 and miR-4644 | Saliva | N = 12 | The relative expression ratios of miR1246 and miR4644 were significantly higher in the cancer group than these ratios in the control group with AUC of 0.814 and 0.763, respectively. | [67] | |
|  | miR-21 and miR-155 | Pancreatic juice | N = 27 | Relative levels of both ex-miR-21 and ex-miR-155 in EVs were significantly higher in PDAC patients compared with chronic CP patients | [68] | |
mRNA | GPC-1 mRNA | Serum | Stage I- II n = 86, stage III-IV n = 32 | GPC1 mRNA was enriched in pancreatic cancer patients and could be used to classify patients with healthy donors with AUC of 1.00 and sensitivity and specificity of 100% | [69] | |
|  | CK18 and CD63 RNA | Plasma | N = 57 | Biomarker panel consisted of miRNA, mRNA, CA19-9, and cell free DNA for PDAC diagnosis achieved an accuracy of92% (95% CI, 86-96%), with sensitivity of 88% (95% CI, 76-95%) and specificity of 95% (95% CI, 88-99%) | [70] | |
|  | Apbb1ip, Aspn, BCO31781, Daf2, Foxp1, Gng2,and Incenp | Saliva | N = 22 (mouse) | The 7 biomarkers were significantly elevated in in pancreatic cancer-bearing mouse saliva when compared with control saliva (P < 0.05) | [71] | |
lncRNA | Sox2ot | Plasma | N = 61 | Sox2ot in sEVs was significantly associated with cancer stages (P = 0.014) and was also related to lymphatic or vascular invasion, showing potential as prognosis marker | [72] | |
|  | HULC | Serum | N = 20 | The expression of HULC in sEVs was significantly higher in PDAC patients than in healthy individuals or IPMN patients with AUC of 0.92 | [73] | |
|  | Malat-1 and CRNDE | Serum | N = 2 | Significantly Higher expression levels of Malat-1 and CRNDE in PDAC-derived sEVs than in healthy donors with P of 0.018 and 0.028 | [74] | |
|  | FGA, KRT19, HIST1H2BK, TIH2,MARCH2, CLDN1, MAL2 and TIMP1 | Plasma | N = 284 | The signature of a combination of 8 RNAs in sEVs showed high accuracy in PDAC detection with AUC of 0.960, 0.950 and 0.936 in the training, internal validation and external validation cohort, respectively. | [75] | |
circRNAs | Circ-IARS | Plasma | N = 40 | Circ-IARS expression was up-regulated in pancreatic cancer tissues and in EVs of patients with metastatic disease with P of 0.015 and 0.002, respectively | [76] | |
|  | Circ-PDE8A | Plasma | N = 60 | High levels of circ-PDE8A were associated with tumor progression and prognosis | [77] | |