Table 2 Summary of EVs as diagnosis biomarkers in pancreatic cancer
Cargo | Sample | Methods for analysis of EVs | Findings | Diagnostic Performance | Refs. |
|---|---|---|---|---|---|
GPC1 | Serum | Flow analysis | The presence of GPC1+ exosomes distinguished healthy subjects and patients with a benign pancreatic disease from patients with early-stage pancreatic cancer | Sensitivity 100%; specificity 100%; AUC 1.0; | [124] |
GPC1 | Serum | Advanced multiplexed plasmonic assay | Sensitivity and specificity of diagnosis are improved significantly when a panel of five markers (EGFR, EPCAM, MUC1, GPC1 and WNT2) are used for PDAC detection | Sensitivity 86%; specificity 81%; diagnostic accuracy 84% | [125] |
GPC1 | Serum | Flow cytometry | Combining diagnostic tools, i.e. GPC1-positive EVs, CA19-9 and EUS-FNA improves all diagnostic performance parameters, and displays the best diagnosis accuracy as high as 84% | Sensitivity 64%; specificity 90%; Diagnosis accuracy 78% | [126] |
GPC1 | Plasma | Flow cytometry | GPC1 as a novel prognostic biomarker for patients with advanced pancreatic cancer following regional intra-arterial chemotherapy treatment | The level of GPC1+ EVs is associated with prognosis | [127] |
EphA2 | Plasma | nanoplasmon-enhanced scattering (nPES) assay | The nPES assay for ephrin type-A receptor 2 (EphA2)-EVs distinguishes pancreatic cancer patients from pancreatitis patients. EphA2-EVs are also predictive in cancer staging and in evaluating responses to neoadjuvant therapy | Sensitivity 94%; | [131] |
ALPPL2 | Cells | quantitative ALISA | Direct and ALPPL2 or CD9 anti-body-based sandwich ALISA were established, which could detect both free and EV-bound forms of ALPPL2 | Not determined | [132] |
O-glycan-binding lectins ABA or ACA | Serum | ExoCounter | EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. The ABA-or ACA-positive EVs were significantly increased in the serum of pancreatic cancer patients | Sensitivity 7.8%; specificity 73.5%; AUC 0.838 | [133] |
Microbiome composition | blood samples | 16S rRNA gene analysis | These microbiome markers, which altered microbial compositions, are candidate biomarkers for early diagnosis of pancreatic cancer with a high area under the receiver operating characteristic curve (0.966 and 1.000, at the phylum and genus level, respectively) | AUC 0.966; | [134] |
EVs-derived RNAs | plasma samples | RT-qPCR | An RNA-ratio based plasma samples including eight EVs-derived RNAs, including FBXO7, MORF4L1, DDX17, TALDO1, AHNAK, TUBA1B, CD44, and SETD3 | AUC 0.89 | [135] |
Zinc transporter protein ZIP4 | Serum | proteomic analysis | The elevated serum levels of exosomal ZIP4 in patients with PDAC showed a diagnostic value of AUC 0.89 | AUC 0.89 | [136] |
MIF | Plasma | ELISA | MIF was higher in exosomes from stage I PDAC patients who later developed liver metastasis and may be a prognostic marker for the development of PDAC liver metastasis | Not determined | [137] |
CD63, Rab5 | Serum | Western Blot | Alteration in the expression level in isolated exosomes of patients with pancreatic cancer was reported for proteins CD63 (3.17 fold) and Rab5 (1.73 fold) | Not determined | [138] |
HULC | Serum | PCR | EVs-encapsulated HULC could be a potential circulating biomarker for early diagnosis PDAC | AUC 0.92 | [139] |